Molecular Neurobiology

, Volume 38, Issue 1, pp 27–65 | Cite as

Review of the Multiple Aspects of Neurofilament Functions, and their Possible Contribution to Neurodegeneration

  • Rodolphe Perrot
  • Raphael Berges
  • Arnaud Bocquet
  • Joel EyerEmail author


Neurofilaments (NF) are the most abundant cytoskeletal component of large myelinated axons from adult central and peripheral nervous system. Here, we provide an overview of the complementary approaches, including biochemistry, cell biology and transgenic technology that were used to investigate the assembly, axonal transport and functions of NF in normal and pathological situations. Following their synthesis and assembly in the cell body, NFs are transported along the axon. This process is finely regulated via phosphorylation of the carboxy-terminal part of the two high-molecular-weight subunits of NF. The correct formation of an axonal network of NF is crucial for the establishment and maintenance of axonal calibre and consequently for the optimisation of conduction velocity. The frequent disorganisation of NF network observed in several neuropathologies support their contribution. However, despite the presence of NF mutations found in some patients, the exact relations between these mutations, the abnormal NF organisation and the pathological process remain a challenging field of investigation.


Neurofilament Intermediate filaments Cytoskeleton Axonal transport Neurodegenerative diseases 



Alzheimer’s disease


amyotrophic lateral sclerosis


bullous pemphigoid antigen 1 neural isoform


calcium–calmodulin-dependent protein kinase II


casein kinase I and II


Charcot-Marie-Tooth disease


central nervous system


giant axonal neuropathy


glycogen synthetase kinase 3


β, β‘-iminodipropionitrile


intermediate filaments


c-Jun N-terminus kinase 1 and 3




myelin-associated glycoprotein


microtubule-associated protein








heavy neurofilament subunit


light neurofilament subunit


medium-sized neurofilament subunit


neurofibrillary tangles


neuronal intermediate filament inclusion disease


O-linked N-acetyl glucosamine


Parkinson’s disease


protein kinase A


protein kinase C


protein kinase N


peripheral nervous system


phosphatase 2A


stress-activated protein kinase


slow component


superoxide dismutase 1


stable tubule only polypeptide


tubulin folding cofactor B



We thank Drs. J.P. Julien and A.C. Peterson for critical reading of this manuscript and helpful scientific suggestions. This work was supported by grants from the Association Française contre les Myopathies, Institut National sur le Cancer and Association pour la Recherche sur la Sclérose en Plaques to J. Eyer.


  1. 1.
    Ishikawa H, Bischoff R, Holtzer H (1968) Mitosis and intermediate-sized filaments in developing skeletal muscle. J Cell Biol 38:538–555PubMedGoogle Scholar
  2. 2.
    Portier MM, de Nechaud B, Gros F (1983) Peripherin, a new member of the intermediate filament protein family. Dev Neurosci 6:335–344PubMedGoogle Scholar
  3. 3.
    Kaplan MP, Chin SS, Fliegner KH, Liem RK (1990) Alpha-internexin, a novel neuronal intermediate filament protein, precedes the low molecular weight neurofilament protein (NF-L) in the developing rat brain. J Neurosci 10:2735–2748PubMedGoogle Scholar
  4. 4.
    Lendahl U, Zimmerman LB, McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60:585–595PubMedGoogle Scholar
  5. 5.
    Julien JP, Mushynski WE (1998) Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol 61:1–23PubMedGoogle Scholar
  6. 6.
    Izmiryan A, Cheraud Y, Khanamiryan L, Leterrier JF, Federici T, Peltekian E, Moura-Neto V, Paulin D, Li Z, Xue ZG (2006) Different expression of synemin isoforms in glia and neurons during nervous system development. Glia 54:204–213PubMedGoogle Scholar
  7. 7.
    Nixon RA, Shea TB (1992) Dynamics of neuronal intermediate filaments: a developmental perspective. Cell Motil Cytoskeleton 22:81–91PubMedGoogle Scholar
  8. 8.
    Herrmann H, Bar H, Kreplak L, Strelkov SV, Aebi U (2007) Intermediate filaments: from cell architecture to nanomechanics. Nat Rev Mol Cell Biol 8:562–573PubMedGoogle Scholar
  9. 9.
    Kim S, Coulombe PA (2007) Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm. Genes Dev 21:1581–1597PubMedGoogle Scholar
  10. 10.
    Oshima RG (2007) Intermediate filaments: a historical perspective. Exp Cell Res 313:1981–1994PubMedGoogle Scholar
  11. 11.
    Beaulieu JM, Robertson J, Julien JP (1999) Interactions between peripherin and neurofilaments in cultured cells: disruption of peripherin assembly by the NF-M and NFH subunits. Biochem Cell Biol 77:41–45PubMedGoogle Scholar
  12. 12.
    Yuan A, Rao MV, Sasaki T, Chen Y, Kumar A, Veeranna, Liem RK, Eyer J, Peterson AC, Julien JP, Nixon RA (2006) Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS. J Neurosci 26:10006–10019PubMedGoogle Scholar
  13. 13.
    Morris JR, Lasek RJ (1982) Stable polymers of the axonal cytoskeleton: the axoplasmic ghost. J Cell Biol 92:192–198PubMedGoogle Scholar
  14. 14.
    Geisler N, Weber K (1981) Self-assembly in Vitro of the 68,000 molecular weight component of the mammalian neurofilament triplet proteins into intermediate-sized filaments. J Mol Biol 151:565–571PubMedGoogle Scholar
  15. 15.
    Liem RK, Hutchison SB (1982) Purification of individual components of the neurofilament triplet: filament assembly from the 70 000-Dalton subunit. Biochemistry 21:3221–3226PubMedGoogle Scholar
  16. 16.
    Gardner EE, Dahl D, Bignami A (1984) Formation of 10-nanometer filaments from the 150 K-Dalton neurofilament protein in vitro. J Neurosci Res 11:145–155PubMedGoogle Scholar
  17. 17.
    Hisanaga S, Hirokawa N (1988) Structure of the peripheral domains of neurofilaments revealed by low angle rotary shadowing. J Mol Biol 202:297–305PubMedGoogle Scholar
  18. 18.
    Hisanaga S, Hirokawa N (1990) Molecular architecture of the neurofilament. II. Reassembly process of neurofilament L protein in vitro. J Mol Biol 211:871–882PubMedGoogle Scholar
  19. 19.
    Carter J, Gragerov A, Konvicka K, Elder G, Weinstein H, Lazzarini RA (1998) Neurofilament (NF) assembly; divergent characteristics of human and rodent NF-L subunits. J Biol Chem 273:5101–5108PubMedGoogle Scholar
  20. 20.
    Jacomy H, Zhu Q, Couillard-Despres S, Beaulieu JM, Julien JP (1999) Disruption of type IV intermediate filament network in mice lacking the neurofilament medium and heavy subunits. J Neurochem 73:972–984PubMedGoogle Scholar
  21. 21.
    Lee MK, Xu Z, Wong PC, Cleveland DW (1993) Neurofilaments are obligate heteropolymers in vivo. J Cell Biol 122:1337–1350PubMedGoogle Scholar
  22. 22.
    Scott D, Smith KE, O’Brien BJ, Angelides KJ (1985) Characterization of mammalian neurofilament triplet proteins. Subunit stoichiometry and morphology of native and reconstituted filaments. J Biol Chem 260:10736–10747PubMedGoogle Scholar
  23. 23.
    Geisler N, Kaufmann E, Fischer S, Plessmann U, Weber K (1983) Neurofilament architecture combines structural principles of intermediate filaments with carboxy terminal extensions increasing in size between triplet proteins. Embo J 2:1295–1302PubMedGoogle Scholar
  24. 24.
    Julien JP, Mushynski WE (1982) Multiple phosphorylation sites in mammalian neurofilament polypeptides. J Biol Chem 257:10467–10470PubMedGoogle Scholar
  25. 25.
    Julien JP, Mushynski WE (1983) The distribution of phosphorylation sites among identified proteolytic fragments of mammalian neurofilaments. J Biol Chem 258:4019–4025PubMedGoogle Scholar
  26. 26.
    Angelides KJ, Smith KE, Takeda M (1989) Assembly and exchange of intermediate filament proteins of neurons: neurofilaments are dynamic structures. J Cell Biol 108:1495–1506PubMedGoogle Scholar
  27. 27.
    Heins S, Wong PC, Muller S, Goldie K, Cleveland DW, Aebi U (1993) The rod domain of NF-L determines neurofilament architecture, whereas the end domains specify filament assembly and network formation. J Cell Biol 123:1517–1533PubMedGoogle Scholar
  28. 28.
    Balin BJ, Clark EA, Trojanowski JQ, Lee VM (1991) Neurofilament reassembly in vitro: biochemical, morphological and immuno-electron microscopic studies employing monoclonal antibodies to defined epitopes. Brain Res 556:181–195PubMedGoogle Scholar
  29. 29.
    Balin BJ, Lee VM (1991) Individual neurofilament subunits reassembled in vitro exhibit unique biochemical, morphological and immunological properties. Brain Res 556:196–208PubMedGoogle Scholar
  30. 30.
    Hirokawa N, Glicksman MA, Willard MB (1984) Organization of mammalian neurofilament polypeptides within the neuronal cytoskeleton. J Cell Biol 98:1523–1536PubMedGoogle Scholar
  31. 31.
    Gill SR, Wong PC, Monteiro MJ, Cleveland DW (1990) Assembly properties of dominant and recessive mutations in the small mouse neurofilament (NF-L) subunit. J Cell Biol 111:2005–2019PubMedGoogle Scholar
  32. 32.
    Wong PC, Cleveland DW (1990) Characterization of dominant and recessive assembly-defective mutations in mouse neurofilament NF-M. J Cell Biol 111:1987–2003PubMedGoogle Scholar
  33. 33.
    Chin SS, Macioce P, Liem RK (1991) Effects of truncated neurofilament proteins on the endogenous intermediate filaments in transfected fibroblasts. J Cell Sci 99(Pt 2):335–350PubMedGoogle Scholar
  34. 34.
    Ching GY, Liem RK (1993) Assembly of type IV neuronal intermediate filaments in nonneuronal cells in the absence of preexisting cytoplasmic intermediate filaments. J Cell Biol 122:1323–1335PubMedGoogle Scholar
  35. 35.
    Ching GY, Liem RK (1999) Analysis of the roles of the head domains of type IV rat neuronal intermediate filament proteins in filament assembly using domain-swapped chimeric proteins. J Cell Sci 112(Pt 13):2233–2240PubMedGoogle Scholar
  36. 36.
    Sihag RK, Nixon RA (1991) Identification of Ser-55 as a major protein kinase A phosphorylation site on the 70-kDa subunit of neurofilaments. Early turnover during axonal transport. J Biol Chem 266:18861–18867PubMedGoogle Scholar
  37. 37.
    Sihag RK, Jaffe H, Nixon RA, Rong X (1999) Serine-23 is a major protein kinase A phosphorylation site on the amino-terminal head domain of the middle molecular mass subunit of neurofilament proteins. J Neurochem 72:491–499PubMedGoogle Scholar
  38. 38.
    Hisanaga S, Gonda Y, Inagaki M, Ikai A, Hirokawa N (1990) Effects of phosphorylation of the neurofilament L protein on filamentous structures. Cell Regul 1:237–248PubMedGoogle Scholar
  39. 39.
    Gibb BJ, Brion JP, Brownlees J, Anderton BH, Miller CC (1998) Neuropathological abnormalities in transgenic mice harbouring a phosphorylation mutant neurofilament transgene. J Neurochem 70:492–500PubMedGoogle Scholar
  40. 40.
    Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y (1996) PKN associates and phosphorylates the head-rod domain of neurofilament protein. J Biol Chem 271:9816–9822PubMedGoogle Scholar
  41. 41.
    Dong DL, Xu ZS, Chevrier MR, Cotter RJ, Cleveland DW, Hart GW (1993) Glycosylation of mammalian neurofilaments. Localization of multiple O-linked N acetyl glucosamine moieties on neurofilament polypeptides L and M. J Biol Chem 268:16679–16687PubMedGoogle Scholar
  42. 42.
    Dong DL, Xu ZS, Hart GW, Cleveland DW (1996) Cytoplasmic O-GlcNAc modification of the head domain and the KSP repeat motif of the neurofilament protein neurofilament-H. J Biol Chem 271:20845–20852PubMedGoogle Scholar
  43. 43.
    Nguyen MD, Shu T, Sanada K, Lariviere RC, Tseng HC, Park SK, Julien JP, Tsai LH (2004) A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons. Nat Cell Biol 6:595–608PubMedGoogle Scholar
  44. 44.
    Leterrier JF, Kas J, Hartwig J, Vegners R, Janmey PA (1996) Mechanical effects of neurofilament cross-bridges. Modulation by phosphorylation, lipids, and interactions with F-actin. J Biol Chem 271:15687–15694PubMedGoogle Scholar
  45. 45.
    Rammensee S, Janmey PA, Bausch AR (2007) Mechanical and structural properties of in vitro neurofilament hydrogels. Eur Biophys J 36:661–668PubMedGoogle Scholar
  46. 46.
    Kreplak L, Bar H, Leterrier JF, Herrmann H, Aebi U (2005) Exploring the mechanical behavior of single intermediate filaments. J Mol Biol 354:569–577PubMedGoogle Scholar
  47. 47.
    Myers MW, Lazzarini RA, Lee VM, Schlaepfer WW, Nelson DL (1987) The human mid-size neurofilament subunit: a repeated protein sequence and the relationship of its gene to the intermediate filament gene family. Embo J 6:1617–1626PubMedGoogle Scholar
  48. 48.
    Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci U S A 99:16899–16903PubMedGoogle Scholar
  49. 49.
    Lees JF, Shneidman PS, Skuntz SF, Carden MJ, Lazzarini RA (1988) The structure and organization of the human heavy neurofilament subunit (NF-H) and the gene encoding it. Embo J 7:1947–1955PubMedGoogle Scholar
  50. 50.
    Thyagarajan A, Strong MJ, Szaro BG (2007) Post-transcriptional control of neurofilaments in development and disease. Exp Cell Res 313:2088–2097PubMedGoogle Scholar
  51. 51.
    Willard M, Simon C (1983) Modulations of neurofilament axonal transport during the development of rabbit retinal ganglion cells. Cell 35:551–559PubMedGoogle Scholar
  52. 52.
    Carden MJ, Trojanowski JQ, Schlaepfer WW, Lee VM (1987) Two-stage expression of neurofilament polypeptides during rat neurogenesis with early establishment of adult phosphorylation patterns. J Neurosci 7:3489–3504PubMedGoogle Scholar
  53. 53.
    Shaw G, Osborn M, Weber K (1981) An immunofluorescence microscopical study of the neurofilament triplet proteins, vimentin and glial fibrillary acidic protein within the adult rat brain. Eur J Cell Biol 26:68–82PubMedGoogle Scholar
  54. 54.
    Shaw G, Weber K (1982) Differential expression of neurofilament triplet proteins in brain development. Nature 298:277–279PubMedGoogle Scholar
  55. 55.
    Pachter JS, Liem RK (1984) The differential appearance of neurofilament triplet polypeptides in the developing rat optic nerve. Dev Biol 103:200–210PubMedGoogle Scholar
  56. 56.
    Zhao Y, Szaro BG (1995) The optic tract and tectal ablation influence the composition of neurofilaments in regenerating optic axons of Xenopus laevis. J Neurosci 15:4629–4640PubMedGoogle Scholar
  57. 57.
    Walker KL, Yoo HK, Undamatla J, Szaro BG (2001) Loss of neurofilaments alters axonal growth dynamics. J Neurosci 21:9655–9666PubMedGoogle Scholar
  58. 58.
    Cuenca N, Fernandez E, de Juan J, Carreres J, Iniguez C (1987) Postnatal development of microtubules and neurofilaments in the rat optic nerve: a quantitative study. J Comp Neurol 263:613–617PubMedGoogle Scholar
  59. 59.
    Breen KC, Anderton BH (1991) Temporal expression of neurofilament polypeptides in differentiating neuroblastoma cells. Neuroreport 2:21–24PubMedGoogle Scholar
  60. 60.
    Giasson BI, Mushynski WE (1997) Study of proline-directed protein kinases involved in phosphorylation of the heavy neurofilament subunit. J Neurosci 17:9466–9472PubMedGoogle Scholar
  61. 61.
    Zhu Q, Couillard-Despres S, Julien JP (1997) Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments. Exp Neurol 148:299–316PubMedGoogle Scholar
  62. 62.
    Elder GA, Friedrich VL Jr, Bosco P, Kang C, Gourov A, Tu PH, Lee VM, Lazzarini RA (1998) Absence of the mid-sized neurofilament subunit decreases axonal calibers, levels of light neurofilament (NF-L), and neurofilament content. J Cell Biol 141:727–739PubMedGoogle Scholar
  63. 63.
    Wong J, Oblinger MM (1987) Changes in neurofilament gene expression occur after axotomy of dorsal root ganglion neurons: an in situ hybridization study. Metab Brain Dis 2:291–303PubMedGoogle Scholar
  64. 64.
    Goldstein ME, Weiss SR, Lazzarini RA, Shneidman PS, Lees JF, Schlaepfer WW (1988) mRNA levels of all three neurofilament proteins decline following nerve transection. Brain Res 427:287–291PubMedGoogle Scholar
  65. 65.
    Oblinger MM, Lasek RJ (1988) Axotomy-induced alterations in the synthesis and transport of neurofilaments and microtubules in dorsal root ganglion cells. J Neurosci 8:1747–1758PubMedGoogle Scholar
  66. 66.
    Mikucki SA, Oblinger MM (1991) Corticospinal neurons exhibit a novel pattern of cytoskeletal gene expression after injury. J Neurosci Res 30:213–225PubMedGoogle Scholar
  67. 67.
    Tetzlaff W, Alexander SW, Miller FD, Bisby MA (1991) Response of facial and rubrospinal neurons to axotomy: changes in mRNA expression for cytoskeletal proteins and GAP-43. J Neurosci 11:2528–2544PubMedGoogle Scholar
  68. 68.
    Hoffman PN, Pollock SC, Striph GG (1993) Altered gene expression after optic nerve transection: reduced neurofilament expression as a general response to axonal injury. Exp Neurol 119:32–36PubMedGoogle Scholar
  69. 69.
    McKerracher L, Essagian C, Aguayo AJ (1993) Temporal changes in beta-tubulin and neurofilament mRNA levels after transection of adult rat retinal ganglion cell axons in the optic nerve. J Neurosci 13:2617–2626PubMedGoogle Scholar
  70. 70.
    Hoffman PN, Lasek RJ (1980) Axonal transport of the cytoskeleton in regenerating motor neurons: constancy and change. Brain Res 202:317–333PubMedGoogle Scholar
  71. 71.
    Hoffman PN, Thompson GW, Griffin JW, Price DL (1985) Changes in neurofilament transport coincide temporally with alterations in the caliber of axons in regenerating motor fibers. J Cell Biol 101:1332–1340PubMedGoogle Scholar
  72. 72.
    Hoffman PN, Cleveland DW (1988) Neurofilament and tubulin expression recapitulates the developmental program during axonal regeneration: induction of a specific beta-tubulin isotype. Proc Natl Acad Sci U S A 85:4530–4533PubMedGoogle Scholar
  73. 73.
    Muma NA, Hoffman PN, Slunt HH, Applegate MD, Lieberburg I, Price DL (1990) Alterations in levels of mRNAs coding for neurofilament protein subunits during regeneration. Exp Neurol 107:230–235PubMedGoogle Scholar
  74. 74.
    Wong J, Oblinger MM (1990) A comparison of peripheral and central axotomy effects on neurofilament and tubulin gene expression in rat dorsal root ganglion neurons. J Neurosci 10:2215–2222PubMedGoogle Scholar
  75. 75.
    Tetzlaff W, Bisby MA, Kreutzberg GW (1988) Changes in cytoskeletal proteins in the rat facial nucleus following axotomy. J Neurosci 8:3181–3189PubMedGoogle Scholar
  76. 76.
    Jiang YQ, Pickett J, Oblinger MM (1994) Comparison of changes in beta-tubulin and NF gene expression in rat DRG neurons under regeneration-permissive and regeneration prohibitive conditions. Brain Res 637:233–241PubMedGoogle Scholar
  77. 77.
    Jacobs AJ, Swain GP, Snedeker JA, Pijak DS, Gladstone LJ, Selzer ME (1997) Recovery of neurofilament expression selectively in regenerating reticulospinal neurons. J Neurosci 17:5206–5220PubMedGoogle Scholar
  78. 78.
    Gervasi C, Thyagarajan A, Szaro BG (2003) Increased expression of multiple neurofilament mRNAs during regeneration of vertebrate central nervous system axons. J Comp Neurol 461:262–275PubMedGoogle Scholar
  79. 79.
    Grant P, Pant HC (2000) Neurofilament protein synthesis and phosphorylation. J Neurocytol 29:843–872PubMedGoogle Scholar
  80. 80.
    Sihag RK, Inagaki M, Yamaguchi T, Shea TB, Pant HC (2007) Role of phosphorylation on the structural dynamics and function of types III and IV intermediate filaments. Exp Cell Res 313:2098–2109PubMedGoogle Scholar
  81. 81.
    Jones SM, Williams RC Jr. (1982) Phosphate content of mammalian neurofilaments. J Biol Chem 257:9902–9905PubMedGoogle Scholar
  82. 82.
    Geisler N, Vandekerckhove J, Weber K (1987) Location and sequence characterization of the major phosphorylation sites of the high molecular mass neurofilament proteins M and H. FEBS Lett 221:403–407PubMedGoogle Scholar
  83. 83.
    Goldstein ME, Sternberger LA, Sternberger NH (1987) Varying degrees of phosphorylation determine microheterogeneity of the heavy neurofilament polypeptide (Nf-H). J Neuroimmunol 14:135–148PubMedGoogle Scholar
  84. 84.
    Lee VM, Otvos L Jr., Carden MJ, Hollosi M, Dietzschold B, Lazzarini RA (1988) Identification of the major multiphosphorylation site in mammalian neurofilaments. Proc Natl Acad Sci U S A 85:1998–2002PubMedGoogle Scholar
  85. 85.
    Pant HC, Veeranna (1995) Neurofilament phosphorylation. Biochem Cell Biol 73:575–592PubMedGoogle Scholar
  86. 86.
    Sternberger LA, Sternberger NH (1983) Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci U S A 80:6126–6130PubMedGoogle Scholar
  87. 87.
    Glicksman MA, Soppet D, Willard MB (1987) Posttranslational modification of neurofilament polypeptides in rabbit retina. J Neurobiol 18:167–196PubMedGoogle Scholar
  88. 88.
    Oblinger MM, Brady ST, McQuarrie IG, Lasek RJ (1987) Cytotypic differences in the protein composition of the axonally transported cytoskeleton in mammalian neurons. J Neurosci 7:453–462PubMedGoogle Scholar
  89. 89.
    Nixon RA, Paskevich PA, Sihag RK, Thayer CY (1994) Phosphorylation on carboxyl terminus domains of neurofilament proteins in retinal ganglion cell neurons in vivo: influences on regional neurofilament accumulation, interneurofilament spacing, and axon caliber. J Cell Biol 126:1031–1046PubMedGoogle Scholar
  90. 90.
    Sihag RK, Jeng AY, Nixon RA (1988) Phosphorylation of neurofilament proteins by protein kinase C. FEBS Lett 233:181–185PubMedGoogle Scholar
  91. 91.
    Sihag RK, Nixon RA (1989) In vivo phosphorylation of distinct domains of the 70-kiloDalton neurofilament subunit involves different protein kinases. J Biol Chem 264:457–464PubMedGoogle Scholar
  92. 92.
    Sihag RK, Nixon RA (1990) Phosphorylation of the amino-terminal head domain of the middle molecular mass 145-kDa subunit of neurofilaments. Evidence for regulation by second messenger-dependent protein kinases. J Biol Chem 265:4166–4171PubMedGoogle Scholar
  93. 93.
    Nixon RA, Lewis SE (1986) Differential turnover of phosphate groups on neurofilament subunits in mammalian neurons in vivo. J Biol Chem 261:16298–16301PubMedGoogle Scholar
  94. 94.
    Nixon RA, Lewis SE, Marotta CA (1987) Posttranslational modification of neurofilament proteins by phosphate during axoplasmic transport in retinal ganglion cell neurons. J Neurosci 7:1145–1158PubMedGoogle Scholar
  95. 95.
    Nixon RA, Lewis SE, Dahl D, Marotta CA, Drager UC (1989) Early posttranslational modifications of the three neurofilament subunits in mouse retinal ganglion cells: neuronal sites and time course in relation to subunit polymerization and axonal transport. Brain Res Mol Brain Res 5:93–108PubMedGoogle Scholar
  96. 96.
    Hashimoto R, Nakamura Y, Goto H, Wada Y, Sakoda S, Kaibuchi K, Inagaki M, Takeda M (1998) Domain- and site-specific phosphorylation of bovine NF-L by Rho associated kinase. Biochem Biophys Res Commun 245:407–411PubMedGoogle Scholar
  97. 97.
    Hashimoto R, Nakamura Y, Komai S, Kashiwagi Y, Tamura K, Goto T, Aimoto S, Kaibuchi K, Shiosaka S, Takeda M (2000) Site-specific phosphorylation of neurofilament-L is mediated by calcium/calmodulin-dependent protein kinase II in the apical dendrites during long-term potentiation. J Neurochem 75:373–382PubMedGoogle Scholar
  98. 98.
    Nixon RA, Brown BA, Marotta CA (1982) Posttranslational modification of a neurofilament protein during axoplasmic transport: implications for regional specialization of CNS axons. J Cell Biol 94:150–158PubMedGoogle Scholar
  99. 99.
    Lewis SE, Nixon RA (1988) Multiple phosphorylated variants of the high molecular mass subunit of neurofilaments in axons of retinal cell neurons: characterization and evidence for their differential association with stationary and moving neurofilaments. J Cell Biol 107:2689–2701PubMedGoogle Scholar
  100. 100.
    Archer DR, Watson DF, Griffin JW (1994) Phosphorylation-dependent immunoreactivity of neurofilaments and the rate of slow axonal transport in the central and peripheral axons of the rat dorsal root ganglion. J Neurochem 62:1119–1125PubMedGoogle Scholar
  101. 101.
    Jung C, Yabe JT, Lee S, Shea TB (2000) Hypophosphorylated neurofilament subunits undergo axonal transport more rapidly than more extensively phosphorylated subunits in situ. Cell Motil Cytoskeleton 47:120–129PubMedGoogle Scholar
  102. 102.
    Ackerley S, Thornhill P, Grierson AJ, Brownlees J, Anderton BH, Leigh PN, Shaw CE, Miller CC (2003) Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments. J Cell Biol 161:489–495PubMedGoogle Scholar
  103. 103.
    Nixon RA, Logvinenko KB (1986) Multiple fates of newly synthesized neurofilament proteins: evidence for a stationary neurofilament network distributed nonuniformly along axons of retinal ganglion cell neurons. J Cell Biol 102:647–659PubMedGoogle Scholar
  104. 104.
    Li BS, Veeranna, Gu J, Grant P, Pant HC (1999) Activation of mitogen-activated protein kinases (Erk1 and Erk2) cascade results in phosphorylation of NF-M tail domains in transfected NIH 3T3 cells. Eur J Biochem 262:211–217PubMedGoogle Scholar
  105. 105.
    Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22:153–183PubMedGoogle Scholar
  106. 106.
    Li BS, Veeranna, Grant P, Pant HC (1999) Calcium influx and membrane depolarization induce phosphorylation of neurofilament (NF-M) KSP repeats in PC12 cells. Brain Res Mol Brain Res 70:84–91PubMedGoogle Scholar
  107. 107.
    Li BS, Zhang L, Gu J, Amin ND, Pant HC (2000) Integrin alpha(1) beta(1)-mediated activation of cyclin-dependent kinase 5 activity is involved in neurite outgrowth and human neurofilament protein H Lys–Ser–Pro tail domain phosphorylation. J Neurosci 20:6055–6062PubMedGoogle Scholar
  108. 108.
    de Waegh SM, Lee VM, Brady ST (1992) Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells. Cell 68:451–463PubMedGoogle Scholar
  109. 109.
    Reles A, Friede RL (1991) Axonal cytoskeleton at the nodes of Ranvier. J Neurocytol 20:450–458PubMedGoogle Scholar
  110. 110.
    Mata M, Kupina N, Fink DJ (1992) Phosphorylation-dependent neurofilament epitopes are reduced at the node of Ranvier. J Neurocytol 21:199–210PubMedGoogle Scholar
  111. 111.
    Hsieh ST, Crawford TO, Griffin JW (1994) Neurofilament distribution and organization in the myelinated axons of the peripheral nervous system. Brain Res 642:316–326PubMedGoogle Scholar
  112. 112.
    Yin X, Crawford TO, Griffin JW, Tu P, Lee VM, Li C, Roder J, Trapp BD (1998) Myelin-associated glycoprotein is a myelin signal that modulates the caliber of myelinated axons. J Neurosci 18:1953–1962PubMedGoogle Scholar
  113. 113.
    Dashiell SM, Tanner SL, Pant HC, Quarles RH (2002) Myelin-associated glycoprotein modulates expression and phosphorylation of neuronal cytoskeletal elements and their associated kinases. J Neurochem 81:1263–1272PubMedGoogle Scholar
  114. 114.
    Lew J, Winkfein RJ, Paudel HK, Wang JH (1992) Brain proline-directed protein kinase is a neurofilament kinase which displays high sequence homology to p34cdc2. J Biol Chem 267:25922–25926PubMedGoogle Scholar
  115. 115.
    Shetty KT, Link WT, Pant HC (1993) cdc2-like kinase from rat spinal cord specifically phosphorylates KSPXK motifs in neurofilament proteins: isolation and characterization. Proc Natl Acad Sci U S A 90:6844–6848PubMedGoogle Scholar
  116. 116.
    Hisanaga S, Uchiyama M, Hosoi T, Yamada K, Honma N, Ishiguro K, Uchida T, Dahl D, Ohsumi K, Kishimoto T (1995) Porcine brain neurofilament-H tail domain kinase: its identification as cdk5/p26 complex and comparison with cdc2/cyclin B kinase. Cell Motil Cytoskeleton 31:283–297PubMedGoogle Scholar
  117. 117.
    Guidato S, Tsai LH, Woodgett J, Miller CC (1996) Differential cellular phosphorylation of neurofilament heavy side-arms by glycogen synthase kinase-3 and cyclin-dependent kinase-5. J Neurochem 66:1698–1706PubMedGoogle Scholar
  118. 118.
    Sun D, Leung CL, Liem RK (1996) Phosphorylation of the high molecular weight neurofilament protein (NF-H) by Cdk5 and p35. J Biol Chem 271:14245–14251PubMedGoogle Scholar
  119. 119.
    Bajaj NP, Miller CC (1997) Phosphorylation of neurofilament heavy-chain side-arm fragments by cyclin-dependent kinase-5 and glycogen synthase kinase-3alpha in transfected cells. J Neurochem 69:737–743PubMedGoogle Scholar
  120. 120.
    Veeranna, Amin ND, Ahn NG, Jaffe H, Winters CA, Grant P, Pant HC (1998) Mitogen-activated protein kinases (Erk1,2) phosphorylate Lys–Ser–Pro (KSP) repeats in neurofilament proteins NF-H and NF-M. J Neurosci 18:4008–4021PubMedGoogle Scholar
  121. 121.
    Sharma M, Sharma P, Pant HC (1999) CDK-5-mediated neurofilament phosphorylation in SHSY5Y human neuroblastoma cells. J Neurochem 73:79–86PubMedGoogle Scholar
  122. 122.
    Miyasaka H, Okabe S, Ishiguro K, Uchida T, Hirokawa N (1993) Interaction of the tail domain of high molecular weight subunits of neurofilaments with the COOH-terminal region of tubulin and its regulation by tau protein kinase II. J Biol Chem 268:22695–22702PubMedGoogle Scholar
  123. 123.
    Brownlees J, Yates A, Bajaj NP, Davis D, Anderton BH, Leigh PN, Shaw CE, Miller CC (2000) Phosphorylation of neurofilament heavy chain side-arms by stress activated protein kinase-1b/Jun N-terminal kinase-3. J Cell Sci 113(Pt 3):401–407PubMedGoogle Scholar
  124. 124.
    Guan RJ, Khatra BS, Cohlberg JA (1991) Phosphorylation of bovine neurofilament proteins by protein kinase FA (glycogen synthase kinase 3). J Biol Chem 266:8262–8267PubMedGoogle Scholar
  125. 125.
    Ackerley S, Grierson AJ, Banner S, Perkinton MS, Brownlees J, Byers HL, Ward M, Thornhill P, Hussain K, Waby JS, Anderton BH, Cooper JD, Dingwall C, Leigh PN, Shaw CE, Miller CC (2004) p38alpha stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis. Mol Cell Neurosci 26:354–364PubMedGoogle Scholar
  126. 126.
    Sasaki T, Gotow T, Shiozaki M, Sakaue F, Saito T, Julien JP, Uchiyama Y, Hisanaga S (2006) Aggregate formation and phosphorylation of neurofilament-L Pro22 Charcot-Marie-Tooth disease mutants. Hum Mol Genet 15:943–952PubMedGoogle Scholar
  127. 127.
    Giasson BI, Mushynski WE (1996) Aberrant stress-induced phosphorylation of perikaryal neurofilaments. J Biol Chem 271:30404–30409PubMedGoogle Scholar
  128. 128.
    O’Ferrall EK, Robertson J, Mushynski WE (2000) Inhibition of aberrant and constitutive phosphorylation of the high-molecular-mass neurofilament subunit by CEP-1347 (KT7515), an inhibitor of the stress-activated protein kinase signaling pathway. J Neurochem 75:2358–2367PubMedGoogle Scholar
  129. 129.
    Dosemeci A, Floyd CC, Pant HC (1990) Characterization of neurofilament-associated protein kinase activities from bovine spinal cord. Cell Mol Neurobiol 10:369–382PubMedGoogle Scholar
  130. 130.
    Floyd CC, Grant P, Gallant PE, Pant HC (1991) Principal neurofilament-associated protein kinase in squid axoplasm is related to casein kinase I. J Biol Chem 266:4987–4994PubMedGoogle Scholar
  131. 131.
    Link WT, Dosemeci A, Floyd CC, Pant HC (1993) Bovine neurofilament-enriched preparations contain kinase activity similar to casein kinase I—neurofilament phosphorylation by casein kinase I (CKI). Neurosci Lett 151:89–93PubMedGoogle Scholar
  132. 132.
    Hollander BA, Bennett GS, Shaw G (1996) Localization of sites in the tail domain of the middle molecular mass neurofilament subunit phosphorylated by a neurofilament-associated kinase and by casein kinase I. J Neurochem 66:412–420PubMedGoogle Scholar
  133. 133.
    Bennett GS, Quintana R (1997) Identification of Ser–Pro and Thr–Pro phosphorylation sites in chicken neurofilament-M tail domain. J Neurochem 68:534–543PubMedGoogle Scholar
  134. 134.
    Xu ZS, Liu WS, Willard M (1990) Identification of serine 473 as a major phosphorylation site in the neurofilament polypeptide NF-L. J Neurosci 10:1838–1846PubMedGoogle Scholar
  135. 135.
    Nakamura Y, Hashimoto R, Kashiwagi Y, Wada Y, Sakoda S, Miyamae Y, Kudo T, Takeda M (1999) Casein kinase II is responsible for phosphorylation of NF-L at Ser-473. FEBS Lett 455:83–86PubMedGoogle Scholar
  136. 136.
    Zheng YL, Li BS, Veeranna, Pant HC (2003) Phosphorylation of the head domain of neurofilament protein (NF-M): a factor regulating topographic phosphorylation of NF-M tail domain KSP sites in neurons. J Biol Chem 278:24026–24032PubMedGoogle Scholar
  137. 137.
    Leterrier JF, Eyer J (1987) Properties of highly viscous gels formed by neurofilaments in vitro. A possible consequence of a specific inter-filament cross-bridging. Biochem J 245:93–101PubMedGoogle Scholar
  138. 138.
    Pant HC (1988) Dephosphorylation of neurofilament proteins enhances their susceptibility to degradation by calpain. Biochem J 256:665–668PubMedGoogle Scholar
  139. 139.
    Sacher MG, Athlan ES, Mushynski WE (1994) Increased phosphorylation of the amino-terminal domain of the low molecular weight neurofilament subunit in okadaic acid-treated neurons. J Biol Chem 269:18480–18484PubMedGoogle Scholar
  140. 140.
    Saito T, Shima H, Osawa Y, Nagao M, Hemmings BA, Kishimoto T, Hisanaga S (1995) Neurofilament-associated protein phosphatase 2A: its possible role in preserving neurofilaments in filamentous states. Biochemistry 34:7376–7384PubMedGoogle Scholar
  141. 141.
    Veeranna, Shetty KT, Link WT, Jaffe H, Wang J, Pant HC (1995) Neuronal cyclin-dependent kinase-5 phosphorylation sites in neurofilament protein (NF-H) are dephosphorylated by protein phosphatase 2A. J Neurochem 64:2681–2690PubMedGoogle Scholar
  142. 142.
    Strack S, Westphal RS, Colbran RJ, Ebner FF, Wadzinski BE (1997) Protein serine/threonine phosphatase 1 and 2A associate with and dephosphorylate neurofilaments. Brain Res Mol Brain Res 49:15–28PubMedGoogle Scholar
  143. 143.
    Slawson C, Hart GW (2003) Dynamic interplay between O-GlcNAc and O-phosphate: the sweet side of protein regulation. Curr Opin Struct Biol 13:631–636PubMedGoogle Scholar
  144. 144.
    Ludemann N, Clement A, Hans VH, Leschik J, Behl C, Brandt R (2005) O-glycosylation of the tail domain of neurofilament protein M in human neurons and in spinal cord tissue of a rat model of amyotrophic lateral sclerosis (ALS). J Biol Chem 280:31648–31658PubMedGoogle Scholar
  145. 145.
    Ryle C, Leow CK, Donaghy M (1997) Nonenzymatic glycation of peripheral and central nervous system proteins in experimental diabetes mellitus. Muscle Nerve 20:577–584PubMedGoogle Scholar
  146. 146.
    Chou SM, Wang HS, Taniguchi A, Bucala R (1998) Advanced glycation end products in neurofilament conglomeration of motoneurons in familial and sporadic amyotrophic lateral sclerosis. Mol Med 4:324–332PubMedGoogle Scholar
  147. 147.
    Suzuki Y, Tanaka M, Sohmiya M, Ichinose S, Omori A, Okamoto K (2005) Identification of nitrated proteins in the normal rat brain using a proteomics approach. Neurol Res 27:630–633PubMedGoogle Scholar
  148. 148.
    Chou SM, Wang HS, Taniguchi A (1996) Role of SOD-1 and nitric oxide/cyclic GMP cascade on neurofilament aggregation in ALS/MND. J Neurol Sci 139(Suppl):16–26PubMedGoogle Scholar
  149. 149.
    Crow JP, Ye YZ, Strong M, Kirk M, Barnes S, Beckman JS (1997) Superoxide dismutase catalyzes nitration of tyrosines by peroxynitrite in the rod and head domains of neurofilament-L. J Neurochem 69:1945–1953PubMedGoogle Scholar
  150. 150.
    Reynolds MR, Berry RW, Binder LI (2007) Nitration in neurodegeneration: deciphering the “Hows” “nYs”. Biochemistry 46:7325–7336PubMedGoogle Scholar
  151. 151.
    Troncoso JC, Costello AC, Kim JH, Johnson GV (1995) Metal-catalyzed oxidation of bovine neurofilaments in vitro. Free Radic Biol Med 18:891–899PubMedGoogle Scholar
  152. 152.
    Kim NH, Jeong MS, Choi SY, Hoon Kang J (2004) Oxidative modification of neurofilament-L by the Cu,Zn-superoxide dismutase and hydrogen peroxide system. Biochimie 86:553–559PubMedGoogle Scholar
  153. 153.
    Gou JP, Leterrier JF (1995) Possible involvement of ubiquitination in neurofilament degradation. Biochem Biophys Res Commun 217:529–538PubMedGoogle Scholar
  154. 154.
    Hoffman PN, Lasek RJ (1975) The slow component of axonal transport. Identification of major structural polypeptides of the axon and their generality among mammalian neurons. J Cell Biol 66:351–366PubMedGoogle Scholar
  155. 155.
    Schlaepfer WW (1974) Calcium-induced degeneration of axoplasm in isolated segments of rat peripheral nerve. Brain Res 69:203–215PubMedGoogle Scholar
  156. 156.
    Millecamps S, Gowing G, Corti O, Mallet J, Julien JP (2007) Conditional NF-L transgene expression in mice for in vivo analysis of turnover and transport rate of neurofilaments. J Neurosci 27:4947–4956PubMedGoogle Scholar
  157. 157.
    Pant HC, Gainer H (1980) Properties of a calcium-activated protease in squid axoplasm which selectively degrades neurofilament proteins. J Neurobiol 11:1–12PubMedGoogle Scholar
  158. 158.
    Schlaepfer WW, Lee C, Lee VM, Zimmerman UJ (1985) An immunoblot study of neurofilament degradation in situ and during calcium-activated proteolysis. J Neurochem 44:502–509PubMedGoogle Scholar
  159. 159.
    Gallant PE, Pant HC, Pruss RM, Gainer H (1986) Calcium-activated proteolysis of neurofilament proteins in the squid giant neuron. J Neurochem 46:1573–1581PubMedGoogle Scholar
  160. 160.
    Perlmutter LS, Gall C, Baudry M, Lynch G (1990) Distribution of calcium-activated protease calpain in the rat brain. J Comp Neurol 296:269–276PubMedGoogle Scholar
  161. 161.
    Eagles PA, Gilbert DS, Maggs A (1981) The location of phosphorylation sites and Ca2+-dependent proteolytic cleavage sites on the major neurofilament polypeptides from Myxicola infundibulum. Biochem J 199:101–111PubMedGoogle Scholar
  162. 162.
    Roots BI (1983) Neurofilament accumulation induced in synapses by leupeptin. Science 221:971–972PubMedGoogle Scholar
  163. 163.
    Schlaepfer WW (1971) Experimental alterations of neurofilaments and neurotubules by calcium and other ions. Exp Cell Res 67:73–80PubMedGoogle Scholar
  164. 164.
    Murachi T, Tanaka K, Hatanaka M, Murakami T (1980) Intracellular Ca2+-dependent protease (calpain) and its high-molecular-weight endogenous inhibitor (calpastatin). Adv Enzyme Regul 19:407–424PubMedGoogle Scholar
  165. 165.
    Murachi T (1990) Calpain and calpastatin. Rinsho Byori 38:337–346PubMedGoogle Scholar
  166. 166.
    Hamakubo T, Kannagi R, Murachi T, Matus A (1986) Distribution of calpains I and II in rat brain. J Neurosci 6:3103–3111PubMedGoogle Scholar
  167. 167.
    Nixon RA, Brown BA, Marotta CA (1983) Limited proteolytic modification of a neurofilament protein involves a proteinase activated by endogenous levels of calcium. Brain Res 275:384–388PubMedGoogle Scholar
  168. 168.
    Nelson WJ, Traub P (1982) Intermediate (10 nm) filament proteins and the Ca2+-activated proteinase specific for vimentin and desmin in the cells from fish to man: an example of evolutionary conservation. J Cell Sci 57:25–49PubMedGoogle Scholar
  169. 169.
    Gitler D, Spira ME (1998) Real time imaging of calcium-induced localized proteolytic activity after axotomy and its relation to growth cone formation. Neuron 20:1123–1135PubMedGoogle Scholar
  170. 170.
    Chin TK, Eagles PA, Maggs A (1983) The proteolytic digestion of ox neurofilaments with trypsin and alpha-chymotrypsin. Biochem J 215:239–252PubMedGoogle Scholar
  171. 171.
    Chin TK, Harding SE, Eagles PA (1989) Characterization of two proteolytically derived soluble polypeptides from the neurofilament triplet components NFM and NFH. Biochem J 264:53–60PubMedGoogle Scholar
  172. 172.
    Malik MN, Fenko MD, Iqbal K, Wisniewski HM (1983) Purification and characterization of two forms of Ca2+-activated neutral protease from calf brain. J Biol Chem 258:8955–8962PubMedGoogle Scholar
  173. 173.
    Nixon RA, Marotta CA (1984) Degradation of neurofilament proteins by purified human brain cathepsin D. J Neurochem 43:507–516PubMedGoogle Scholar
  174. 174.
    Banay-Schwartz M, Dahl D, Hui KS, Lajtha A (1987) The breakdown of the individual neurofilament proteins by cathepsin D. Neurochem Res 12:361–367PubMedGoogle Scholar
  175. 175.
    Suzuki H, Takeda M, Nakamura Y, Kato Y, Tada K, Hariguchi S, Nishimura T (1988) Neurofilament degradation by bovine brain cathepsin D. Neurosci Lett 89:240–245PubMedGoogle Scholar
  176. 176.
    Traub P, Vorgias CE, Nelson WJ (1985) Interaction in vitro of the neurofilament triplet proteins from porcine spinal cord with natural RNA and DNA. Mol Biol Rep 10:129–136PubMedGoogle Scholar
  177. 177.
    Wang Q, Tolstonog GV, Shoeman R, Traub P (2001) Sites of nucleic acid binding in type I-IV intermediate filament subunit proteins. Biochemistry 40:10342–10349PubMedGoogle Scholar
  178. 178.
    Goldstein ME, Sternberger NH, Sternberger LA (1987) Phosphorylation protects neurofilaments against proteolysis. J Neuroimmunol 14:149–160PubMedGoogle Scholar
  179. 179.
    Bizzi A, Crane RC, Autilio-Gambetti L, Gambetti P (1984) Aluminum effect on slow axonal transport: a novel impairment of neurofilament transport. J Neurosci 4:722–731PubMedGoogle Scholar
  180. 180.
    Troncoso JC, Sternberger NH, Sternberger LA, Hoffman PN, Price DL (1986) Immunocytochemical studies of neurofilament antigens in the neurofibrillary pathology induced by aluminum. Brain Res 364:295–300PubMedGoogle Scholar
  181. 181.
    Nixon RA, Clarke JF, Logvinenko KB, Tan MK, Hoult M, Grynspan F (1990) Aluminum inhibits calpain-mediated proteolysis and induces human neurofilament proteins to form protease-resistant high molecular weight complexes. J Neurochem 55:1950–1959PubMedGoogle Scholar
  182. 182.
    Posmantur R, Hayes RL, Dixon CE, Taft WC (1994) Neurofilament 68 and neurofilament 200 protein levels decrease after traumatic brain injury. J Neurotrauma 11:533–545PubMedGoogle Scholar
  183. 183.
    Banik NL, Matzelle DC, Gantt-Wilford G, Osborne A, Hogan EL (1997) Increased calpain content and progressive degradation of neurofilament protein in spinal cord injury. Brain Res 752:301–306PubMedGoogle Scholar
  184. 184.
    Bahmanyar S, Moreau-Dubois MC, Brown P, Cathala F, Gajdusek DC (1983) Serum antibodies to neurofilament antigens in patients with neurological and other diseases and in healthy controls. J Neuroimmunol 5:191–196PubMedGoogle Scholar
  185. 185.
    Elizan TS, Casals J, Yahr MD (1983) Antineurofilament antibodies in postencephalitic and idiopathic Parkinson’s disease. J Neurol Sci 59:341–347PubMedGoogle Scholar
  186. 186.
    Stefansson K, Marton LS, Dieperink ME, Molnar GK, Schlaepfer WW, Helgason CM (1985) Circulating autoantibodies to the 200,000-Dalton protein of neurofilaments in the serum of healthy individuals. Science 228:1117–1119PubMedGoogle Scholar
  187. 187.
    Toh BH, Gibbs CJ Jr., Gajdusek DC, Tuthill DD, Dahl D (1985) The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from chimpanzees with kuru or Creutzfeldt-Jakob disease; a 62-kDa neurofilament-associated protein reacts with sera from sheep with natural scrapie. Proc Natl Acad Sci U S A 82:3894–3896PubMedGoogle Scholar
  188. 188.
    Hirano A (1991) Cytopathology of amyotrophic lateral sclerosis. Adv Neurol 56:91–101PubMedGoogle Scholar
  189. 189.
    Corbo M, Hays AP (1992) Peripherin and neurofilament protein coexist in spinal spheroids of motor neuron disease. J Neuropathol Exp Neurol 51:531–537PubMedGoogle Scholar
  190. 190.
    Hill WD, Arai M, Cohen JA, Trojanowski JQ (1993) Neurofilament mRNA is reduced in Parkinson’s disease substantia nigra pars compacta neurons. J Comp Neurol 329:328–336PubMedGoogle Scholar
  191. 191.
    Leigh PN, Dodson A, Swash M, Brion JP, Anderton BH (1989) Cytoskeletal abnormalities in motor neuron disease. An immunocytochemical study. Brain 112(Pt 2):521–535PubMedGoogle Scholar
  192. 192.
    Chou SM, Hartmann HA (1965) Electron microscopy of focal neuroaxonal lesions produced by beta-beta-iminodipropionitrile (IDPN) in rats. I. The advanced lesions. Acta Neuropathol 4:590–603PubMedGoogle Scholar
  193. 193.
    Kadota T, Kadota K (1978) Neurofilament hypertrophy induced in the rabbit spinal cord after intracisternal injection of aluminum chloride (author’s transl). J Toxicol Sci 3:57–67PubMedGoogle Scholar
  194. 194.
    Papasozomenos SC, Autilio-Gambetti L, Gambetti P (1981) Reorganization of axoplasmic organelles following beta, beta’-iminodipropionitrile administration. J Cell Biol 91:866–871PubMedGoogle Scholar
  195. 195.
    Gold BG, Griffin JW, Price DL (1985) Slow axonal transport in acrylamide neuropathy: different abnormalities produced by single-dose and continuous administration. J Neurosci 5:1755–1768PubMedGoogle Scholar
  196. 196.
    Gschwend TP, Krueger SR, Kozlov SV, Wolfer DP, Sonderegger P (1997) Neurotrypsin, a novel multidomain serine protease expressed in the nervous system. Mol Cell Neurosci 9:207–219PubMedGoogle Scholar
  197. 197.
    Yamashiro K, Tsuruoka N, Kodama S, Tsujimoto M, Yamamura Y, Tanaka T, Nakazato H, Yamaguchi N (1997) Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain. Biochim Biophys Acta 1350:11–14PubMedGoogle Scholar
  198. 198.
    Scarisbrick IA, Isackson PJ, Ciric B, Windebank AJ, Rodriguez M (2001) MSP, a trypsin-like serine protease, is abundantly expressed in the human nervous system. J Comp Neurol 431:347–361PubMedGoogle Scholar
  199. 199.
    Chou SM, Taniguchi A, Wang HS, Festoff BW (1998) Serpin = serine protease-like complexes within neurofilament conglomerates of motoneurons in amyotrophic lateral sclerosis. J Neurol Sci 160(Suppl 1):S73–79PubMedGoogle Scholar
  200. 200.
    Tsuji T, Shimohama S, Kimura J, Shimizu K (1998) m-Calpain (calcium-activated neutral proteinase) in Alzheimer’s disease brains. Neurosci Lett 248:109–112PubMedGoogle Scholar
  201. 201.
    Fasani F, Bocquet A, Robert P, Peterson A, Eyer J (2004) The amount of neurofilaments aggregated in the cell body is controlled by their increased sensitivity to trypsin-like proteases. J Cell Sci 117:861–869PubMedGoogle Scholar
  202. 202.
    Eyer J, Peterson A (1994) Neurofilament-deficient axons and perikaryal aggregates in viable transgenic mice expressing a neurofilament-beta-galactosidase fusion protein. Neuron 12:389–405PubMedGoogle Scholar
  203. 203.
    Runge MS, Laue TM, Yphantis DA, Lifsics MR, Saito A, Altin M, Reinke K, Williams RC Jr. (1981) ATP-induced formation of an associated complex between microtubules and neurofilaments. Proc Natl Acad Sci U S A 78:1431–1435PubMedGoogle Scholar
  204. 204.
    Leterrier JF, Wong J, Liem RK, Shelanski ML (1984) Promotion of microtubule assembly by neurofilament-associated microtubule-associated proteins. J Neurochem 43:1385–1391PubMedGoogle Scholar
  205. 205.
    Aamodt EJ, Williams RC Jr. (1984) Association of microtubules and neurofilaments in vitro is not mediated by ATP. Biochemistry 23:6031–6035PubMedGoogle Scholar
  206. 206.
    Heimann R, Shelanski ML, Liem RK (1985) Microtubule-associated proteins bind specifically to the 70-kDa neurofilament protein. J Biol Chem 260:12160–12166PubMedGoogle Scholar
  207. 207.
    Flynn G, Purich DL (1987) GTP regeneration influences interactions of microtubules, neurofilaments, and microtubule-associated proteins in vitro. J Biol Chem 262:15443–15447PubMedGoogle Scholar
  208. 208.
    Minami Y, Sakai H (1983) Network formation by neurofilament-induced polymerization of tubulin: 200 K subunit of neurofilament triplet promotes nucleation of tubulin polymerization and enhances microtubule assembly. J Biochem 94:2023–2033PubMedGoogle Scholar
  209. 209.
    Minami Y, Endo S, Sakai H (1984) Participation of 200 K or 150 K subunit of neurofilament in construction of the filament core with 70 K subunit and promotion of tubulin polymerization by incorporated 200 K subunit. J Biochem 96:1481–1490PubMedGoogle Scholar
  210. 210.
    Hirokawa N (1982) Cross-linker system between neurofilaments, microtubules, and membranous organelles in frog axons revealed by the quick-freeze, deep-etching method. J Cell Biol 94:129–142PubMedGoogle Scholar
  211. 211.
    Job D, Rauch CT, Fischer EH, Margolis RL (1982) Recycling of cold-stable microtubules: evidence that cold stability is due to substoichiometric polymer blocks. Biochemistry 21:509–515PubMedGoogle Scholar
  212. 212.
    Denarier E, Fourest-Lieuvin A, Bosc C, Pirollet F, Chapel A, Margolis RL, Job D (1998) Nonneuronal isoforms of STOP protein are responsible for microtubule cold stability in mammalian fibroblasts. Proc Natl Acad Sci U S A 95:6055–6060PubMedGoogle Scholar
  213. 213.
    Job D, Fischer EH, Margolis RL (1981) Rapid disassembly of cold-stable microtubules by calmodulin. Proc Natl Acad Sci U S A 78:4679–4682PubMedGoogle Scholar
  214. 214.
    Margolis RL, Rauch CT, Job D (1986) Purification and assay of a 145-kDa protein (STOP145) with microtubule-stabilizing and motility behavior. Proc Natl Acad Sci U S A 83:639–643PubMedGoogle Scholar
  215. 215.
    Bosc C, Cronk JD, Pirollet F, Watterson DM, Haiech J, Job D, Margolis RL (1996) Cloning, expression, and properties of the microtubule-stabilizing protein STOP. Proc Natl Acad Sci U S A 93:2125–2130PubMedGoogle Scholar
  216. 216.
    Pirollet F, Rauch CT, Job D, Margolis RL (1989) Monoclonal antibody to microtubule-associated STOP protein: affinity purification of neuronal STOP activity and comparison of antigen with activity in neuronal and nonneuronal cell extracts. Biochemistry 28:835–842PubMedGoogle Scholar
  217. 217.
    Pirollet F, Derancourt J, Haiech J, Job D, Margolis RL (1992) Ca(2+)-calmodulin regulated effectors of microtubule stability in bovine brain. Biochemistry 31:8849–8855PubMedGoogle Scholar
  218. 218.
    Guillaud L, Bosc C, Fourest-Lieuvin A, Denarier E, Pirollet F, Lafanechere L, Job D (1998) STOP proteins are responsible for the high degree of microtubule stabilization observed in neuronal cells. J Cell Biol 142:167–179PubMedGoogle Scholar
  219. 219.
    Letournel F, Bocquet A, Dubas F, Barthelaix A, Eyer J (2003) Stable tubule only polypeptides (STOP) proteins co-aggregate with spheroid neurofilaments in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 62:1211–1219PubMedGoogle Scholar
  220. 220.
    Yabe JT, Pimenta A, Shea TB (1999) Kinesin-mediated transport of neurofilament protein oligomers in growing axons. J Cell Sci 112(Pt 21):3799–3814PubMedGoogle Scholar
  221. 221.
    Yabe JT, Jung C, Chan WK, Shea TB (2000) Phospho-dependent association of neurofilament proteins with kinesin in situ. Cell Motil Cytoskeleton 45:249–262PubMedGoogle Scholar
  222. 222.
    Shah JV, Flanagan LA, Janmey PA, Leterrier JF (2000) Bidirectional translocation of neurofilaments along microtubules mediated in part by dynein/dynactin. Mol Biol Cell 11:3495–3508PubMedGoogle Scholar
  223. 223.
    Wagner OI, Ascano J, Tokito M, Leterrier JF, Janmey PA, Holzbaur EL (2004) The interaction of neurofilaments with the microtubule motor cytoplasmic dynein. Mol Biol Cell 15:5092–5100PubMedGoogle Scholar
  224. 224.
    Theiss C, Napirei M, Meller K (2005) Impairment of anterograde and retrograde neurofilament transport after anti-kinesin and anti-dynein antibody microinjection in chicken dorsal root ganglia. Eur J Cell Biol 84:29–43PubMedGoogle Scholar
  225. 225.
    Motil J, Chan WK, Dubey M, Chaudhury P, Pimenta A, Chylinski TM, Ortiz DT, Shea TB (2006) Dynein mediates retrograde neurofilament transport within axons and anterograde delivery of NF from perikarya into axons: regulation by multiple phosphorylation events. Cell Motil Cytoskeleton 63:266–286PubMedGoogle Scholar
  226. 226.
    Hirokawa N (1998) Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279:519–526PubMedGoogle Scholar
  227. 227.
    Goldenring JR, Lasher RS, Vallano ML, Ueda T, Naito S, Sternberger NH, Sternberger LA, DeLorenzo RJ (1986) Association of synapsin I with neuronal cytoskeleton. Identification in cytoskeletal preparations in vitro and immunocytochemical localization in brain of synapsin I. J Biol Chem 261:8495–8504PubMedGoogle Scholar
  228. 228.
    Steiner JP, Ling E, Bennett V (1987) Nearest neighbor analysis for brain synapsin I. Evidence from in vitro reassociation assays for association with membrane protein(s) and the Mr = 68,000 neurofilament subunit. J Biol Chem 262:905–914PubMedGoogle Scholar
  229. 229.
    Yang Y, Dowling J, Yu QC, Kouklis P, Cleveland DW, Fuchs E (1996) An essential cytoskeletal linker protein connecting actin microfilaments to intermediate filaments. Cell 86:655–665PubMedGoogle Scholar
  230. 230.
    Guo L, Degenstein L, Dowling J, Yu QC, Wollmann R, Perman B, Fuchs E (1995) Gene targeting of BPAG1: abnormalities in mechanical strength and cell migration in stratified epithelia and neurologic degeneration. Cell 81:233–243PubMedGoogle Scholar
  231. 231.
    Brown A, Bernier G, Mathieu M, Rossant J, Kothary R (1995) The mouse dystonia musculorum gene is a neural isoform of bullous pemphigoid antigen 1. Nat Genet 10:301–306PubMedGoogle Scholar
  232. 232.
    Eyer J, Cleveland DW, Wong PC, Peterson AC (1998) Pathogenesis of two axonopathies does not require axonal neurofilaments. Nature 391:584–587PubMedGoogle Scholar
  233. 233.
    Yang Y, Bauer C, Strasser G, Wollman R, Julien JP, Fuchs E (1999) Integrators of the cytoskeleton that stabilize microtubules. Cell 98:229–238PubMedGoogle Scholar
  234. 234.
    Leung CL, Zheng M, Prater SM, Liem RK (2001) The BPAG1 locus: alternative splicing produces multiple isoforms with distinct cytoskeletal linker domains, including predominant isoforms in neurons and muscles. J Cell Biol 154:691–697PubMedGoogle Scholar
  235. 235.
    Young KG, Kothary R (2007) Dystonin/Bpag1—a link to what? Cell Motil Cytoskeleton 64:897–905PubMedGoogle Scholar
  236. 236.
    Metuzals J, Mushynski WE (1974) Electron microscope and experimental investigations of the neurofilamentous network in Deiters’ neurons. Relationship with the cell surface and nuclear pores. J Cell Biol 61:701–722PubMedGoogle Scholar
  237. 237.
    Traub P, Perides G, Kuhn S, Scherbarth A (1987) Interaction in vitro of non-epithelial intermediate filament proteins with histones. Z Naturforsch [C] 42:47–63Google Scholar
  238. 238.
    Metuzals J, Fishman HM, Robb IA (1995) The neurofilamentous network-smooth endoplasmic reticulum complex in transected squid giant axon. Biol Bull 189:216–218PubMedGoogle Scholar
  239. 239.
    Leterrier JF, Rusakov DA, Nelson BD, Linden M (1994) Interactions between brain mitochondria and cytoskeleton: evidence for specialized outer membrane domains involved in the association of cytoskeleton-associated proteins to mitochondria in situ and in vitro. Microsc Res Tech 27:233–261PubMedGoogle Scholar
  240. 240.
    Morris RL, Hollenbeck PJ (1995) Axonal transport of mitochondria along microtubules and F-actin in living vertebrate neurons. J Cell Biol 131:1315–1326PubMedGoogle Scholar
  241. 241.
    Straube-West K, Loomis PA, Opal P, Goldman RD (1996) Alterations in neural intermediate filament organization: functional implications and the induction of pathological changes related to motor neuron disease. J Cell Sci 109(Pt 9):2319–2329PubMedGoogle Scholar
  242. 242.
    Szebenyi G, Smith GM, Li P, Brady ST (2002) Overexpression of neurofilament H disrupts normal cell structure and function. J Neurosci Res 68:185–198PubMedGoogle Scholar
  243. 243.
    Wagner OI, Lifshitz J, Janmey PA, Linden M, McIntosh TK, Leterrier JF (2003) Mechanisms of mitochondria-neurofilament interactions. J Neurosci 23:9046–9058PubMedGoogle Scholar
  244. 244.
    Friede RL, Samorajski T (1970) Axon caliber related to neurofilaments and microtubules in sciatic nerve fibers of rats and mice. Anat Rec 167:379–387PubMedGoogle Scholar
  245. 245.
    Hoffman PN, Griffin JW, Price DL (1984) Control of axonal caliber by neurofilament transport. J Cell Biol 99:705–714PubMedGoogle Scholar
  246. 246.
    Sanchez I, Hassinger L, Paskevich PA, Shine HD, Nixon RA (1996) Oligodendroglia regulate the regional expansion of axon caliber and local accumulation of neurofilaments during development independently of myelin formation. J Neurosci 16:5095–5105PubMedGoogle Scholar
  247. 247.
    Yamasaki H, Itakura C, Mizutani M (1991) Hereditary hypotrophic axonopathy with neurofilament deficiency in a mutant strain of the Japanese quail. Acta Neuropathol 82:427–434PubMedGoogle Scholar
  248. 248.
    Yamasaki H, Bennett GS, Itakura C, Mizutani M (1992) Defective expression of neurofilament protein subunits in hereditary hypotrophic axonopathy of quail. Lab Invest 66:734–743PubMedGoogle Scholar
  249. 249.
    Ohara O, Gahara Y, Miyake T, Teraoka H, Kitamura T (1993) Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene. J Cell Biol 121:387–395PubMedGoogle Scholar
  250. 250.
    Cote F, Collard JF, Julien JP (1993) Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. Cell 73:35–46PubMedGoogle Scholar
  251. 251.
    Perrot R, Lonchampt P, Peterson AC, Eyer J (2007) Axonal neurofilaments control multiple fiber properties but do not influence structure or spacing of nodes of Ranvier. J Neurosci 27:9573–9584PubMedGoogle Scholar
  252. 252.
    Monteiro MJ, Hoffman PN, Gearhart JD, Cleveland DW (1990) Expression of NF-L in both neuronal and nonneuronal cells of transgenic mice: increased neurofilament density in axons without affecting caliber. J Cell Biol 111:1543–1557PubMedGoogle Scholar
  253. 253.
    Xu Z, Marszalek JR, Lee MK, Wong PC, Folmer J, Crawford TO, Hsieh ST, Griffin JW, Cleveland DW (1996) Subunit composition of neurofilaments specifies axonal diameter. J Cell Biol 133:1061–1069PubMedGoogle Scholar
  254. 254.
    Nguyen MD, Lariviere RC, Julien JP (2000) Reduction of axonal caliber does not alleviate motor neuron disease caused by mutant superoxide dismutase 1. Proc Natl Acad Sci U S A 97:12306–12311PubMedGoogle Scholar
  255. 255.
    Meier J, Couillard-Despres S, Jacomy H, Gravel C, Julien JP (1999) Extra neurofilament NF-L subunits rescue motor neuron disease caused by overexpression of the human NF-H gene in mice. J Neuropathol Exp Neurol 58:1099–1110PubMedGoogle Scholar
  256. 256.
    Elder GA, Friedrich VL Jr., Kang C, Bosco P, Gourov A, Tu PH, Zhang B, Lee VM, Lazzarini RA (1998) Requirement of heavy neurofilament subunit in the development of axons with large calibers. J Cell Biol 143:195–205PubMedGoogle Scholar
  257. 257.
    Rao MV, Houseweart MK, Williamson TL, Crawford TO, Folmer J, Cleveland DW (1998) Neurofilament-dependent radial growth of motor axons and axonal organization of neurofilaments does not require the neurofilament heavy subunit (NF-H) or its phosphorylation. J Cell Biol 143:171–181PubMedGoogle Scholar
  258. 258.
    Zhu Q, Lindenbaum M, Levavasseur F, Jacomy H, Julien JP (1998) Disruption of the NF-H gene increases axonal microtubule content and velocity of neurofilament transport: relief of axonopathy resulting from the toxin beta,beta’-iminodipropionitrile. J Cell Biol 143:183–193PubMedGoogle Scholar
  259. 259.
    Hirokawa N, Takeda S (1998) Gene targeting studies begin to reveal the function of neurofilament proteins. J Cell Biol 143:1–4PubMedGoogle Scholar
  260. 260.
    Gotow T, Takeda M, Tanaka T, Hashimoto PH (1992) Macromolecular structure of reassembled neurofilaments as revealed by the quick-freeze deep-etch mica method: difference between NF-M and NF-H subunits in their ability to form cross-bridges. Eur J Cell Biol 58:331–345PubMedGoogle Scholar
  261. 261.
    Brown HG, Hoh JH (1997) Entropic exclusion by neurofilament sidearms: a mechanism for maintaining interfilament spacing. Biochemistry 36:15035–15040PubMedGoogle Scholar
  262. 262.
    Kumar S, Hoh JH (2004) Modulation of repulsive forces between neurofilaments by sidearm phosphorylation. Biochem Biophys Res Commun 324:489–496PubMedGoogle Scholar
  263. 263.
    Aranda-Espinoza H, Carl P, Leterrier JF, Janmey P, Discher DE (2002) Domain unfolding in neurofilament sidearms: effects of phosphorylation and ATP. FEBS Lett 531:397–401PubMedGoogle Scholar
  264. 264.
    Wong PC, Marszalek J, Crawford TO, Xu Z, Hsieh ST, Griffin JW, Cleveland DW (1995) Increasing neurofilament subunit NF-M expression reduces axonal NF-H, inhibits radial growth, and results in neurofilamentous accumulation in motor neurons. J Cell Biol 130:1413–1422PubMedGoogle Scholar
  265. 265.
    Marszalek JR, Williamson TL, Lee MK, Xu Z, Hoffman PN, Becher MW, Crawford TO, Cleveland DW (1996) Neurofilament subunit NF-H modulates axonal diameter by selectively slowing neurofilament transport. J Cell Biol 135:711–724PubMedGoogle Scholar
  266. 266.
    Rao MV, Garcia ML, Miyazaki Y, Gotow T, Yuan A, Mattina S, Ward CM, Calcutt NA, Uchiyama Y, Nixon RA, Cleveland DW (2002) Gene replacement in mice reveals that the heavily phosphorylated tail of neurofilament heavy subunit does not affect axonal caliber or the transit of cargoes in slow axonal transport. J Cell Biol 158:681–693PubMedGoogle Scholar
  267. 267.
    Garcia ML, Lobsiger CS, Shah SB, Deerinck TJ, Crum J, Young D, Ward CM, Crawford TO, Gotow T, Uchiyama Y, Ellisman MH, Calcutt NA, Cleveland DW (2003) NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth. J Cell Biol 163:1011–1020PubMedGoogle Scholar
  268. 268.
    Rao MV, Campbell J, Yuan A, Kumar A, Gotow T, Uchiyama Y, Nixon RA (2003) The neurofilament middle molecular mass subunit carboxyl-terminal tail domains is essential for the radial growth and cytoskeletal architecture of axons but not for regulating neurofilament transport rate. J Cell Biol 163:1021–1031PubMedGoogle Scholar
  269. 269.
    Windebank AJ, Wood P, Bunge RP, Dyck PJ (1985) Myelination determines the caliber of dorsal root ganglion neurons in culture. J Neurosci 5:1563–1569PubMedGoogle Scholar
  270. 270.
    Aguayo AJ, Attiwell M, Trecarten J, Perkins S, Bray GM (1977) Abnormal myelination in transplanted Trembler mouse Schwann cells. Nature 265:73–75PubMedGoogle Scholar
  271. 271.
    Pollard JD, McLeod JG (1980) Nerve grafts in the Trembler mouse. An electrophysiological and histological study. J Neurol Sci 46:373–383PubMedGoogle Scholar
  272. 272.
    Kirkpatrick LL, Witt AS, Payne HR, Shine HD, Brady ST (2001) Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axons. J Neurosci 21:2288–2297PubMedGoogle Scholar
  273. 273.
    Sternberger NH, Quarles RH, Itoyama Y, Webster HD (1979) Myelin-associated glycoprotein demonstrated immunocytochemically in myelin and myelin-forming cells of developing rat. Proc Natl Acad Sci U S A 76:1510–1514PubMedGoogle Scholar
  274. 274.
    Trapp BD, Andrews SB, Cootauco C, Quarles R (1989) The myelin-associated glycoprotein is enriched in multivesicular bodies and periaxonal membranes of actively myelinating oligodendrocytes. J Cell Biol 109:2417–2426PubMedGoogle Scholar
  275. 275.
    Lunn MP, Crawford TO, Hughes RA, Griffin JW, Sheikh KA (2002) Anti-myelin-associated glycoprotein antibodies alter neurofilament spacing. Brain 125:904–911PubMedGoogle Scholar
  276. 276.
    Gasser HS, Grundfest H (1939) Axon diameters in relation to the spike dimensions and the conduction velocity in mammalian A fibers. Am J Physiol 127:393–414Google Scholar
  277. 277.
    Hursh JB (1939) Conduction velocity and diameter of nerve fibers. Am J Physiol 127:131–139Google Scholar
  278. 278.
    Hutchinson NA, Koles ZJ, Smith RS (1970) Conduction velocity in myelinated nerve fibres of Xenopus laevis. J Physiol 208:279–289PubMedGoogle Scholar
  279. 279.
    Huxley AF, Stampfli R (1949) Evidence for saltatory conduction in peripheral myelinated nerve fibres. J Physiol 108:315–339Google Scholar
  280. 280.
    Goldman L, Albus JS (1968) Computation of impulse conduction in myelinated fibers; theoretical basis of the velocity-diameter relation. Biophys J 8:596–607PubMedGoogle Scholar
  281. 281.
    Brill MH, Waxman SG, Moore JW, Joyner RW (1977) Conduction velocity and spike configuration in myelinated fibres: computed dependence on internode distance. J Neurol Neurosurg Psychiatry 40:769–774PubMedGoogle Scholar
  282. 282.
    Court FA, Sherman DL, Pratt T, Garry EM, Ribchester RR, Cottrell DF, Fleetwood-Walker SM, Brophy PJ (2004) Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves. Nature 431:191–195PubMedGoogle Scholar
  283. 283.
    Rushton WA (1951) A theory of the effects of fibre size in medullated nerve. J Physiol 115:101–122PubMedGoogle Scholar
  284. 284.
    Hodgkin AL (1964) The ionic basis of nervous conduction. Science 145:1148–1154PubMedGoogle Scholar
  285. 285.
    Smith RS, Koles ZJ (1970) Myelinated nerve fibers: computed effect of myelin thickness on conduction velocity. Am J Physiol 219:1256–1258PubMedGoogle Scholar
  286. 286.
    Bhat MA, Rios JC, Lu Y, Garcia-Fresco GP, Ching W, St Martin M, Li J, Einheber S, Chesler M, Rosenbluth J, Salzer JL, Bellen HJ (2001) Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/Paranodin. Neuron 30:369–383PubMedGoogle Scholar
  287. 287.
    Boyle ME, Berglund EO, Murai KK, Weber L, Peles E, Ranscht B (2001) Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve. Neuron 30:385–397PubMedGoogle Scholar
  288. 288.
    Murray JA, Blakemore WF (1980) The relationship between internodal length and fibre diameter in the spinal cord of the cat. J Neurol Sci 45:29–41PubMedGoogle Scholar
  289. 289.
    Friede RL, Meier T, Diem M (1981) How is the exact length of an internode determined. J Neurol Sci 50:217–228PubMedGoogle Scholar
  290. 290.
    Fried K, Hildebrand C, Erdelyi G (1982) Myelin sheath thickness and internodal length of nerve fibres in the developing feline inferior alveolar nerve. J Neurol Sci 54:47–57PubMedGoogle Scholar
  291. 291.
    Sakaguchi T, Okada M, Kitamura T, Kawasaki K (1993) Reduced diameter and conduction velocity of myelinated fibers in the sciatic nerve of a neurofilament-deficient mutant quail. Neurosci Lett 153:65–68PubMedGoogle Scholar
  292. 292.
    Kriz J, Zhu Q, Julien JP, Padjen AL (2000) Electrophysiological properties of axons in mice lacking neurofilament subunit genes: disparity between conduction velocity and axon diameter in absence of NF-H. Brain Res 885:32–44PubMedGoogle Scholar
  293. 293.
    Kriz J, Meier J, Julien JP, Padjen AL (2000) Altered ionic conductances in axons of transgenic mouse expressing the human neurofilament heavy gene: A mouse model of amyotrophic lateral sclerosis. Exp Neurol 163:414–421PubMedGoogle Scholar
  294. 294.
    Zochodne DW, Sun HS, Cheng C, Eyer J (2004) Accelerated diabetic neuropathy in axons without neurofilaments. Brain 127:2193–2200PubMedGoogle Scholar
  295. 295.
    Sheykholeslami K, Kaga K, Mizutani M (2001) Auditory nerve fiber differences in the normal and neurofilament deficient Japanese quail. Hear Res 159:117–124PubMedGoogle Scholar
  296. 296.
    Elder GA, Friedrich VL Jr., Lazzarini RA (2001) Schwann cells and oligodendrocytes read distinct signals in establishing myelin sheath thickness. J Neurosci Res 65:493–499PubMedGoogle Scholar
  297. 297.
    Berthold CH, Rydmark M (1983) Electron microscopic serial section analysis of nodes of Ranvier in lumbosacral spinal roots of the cat: ultrastructural organization of nodal compartments in fibres of different sizes. J Neurocytol 12:475–505PubMedGoogle Scholar
  298. 298.
    Hildebrand C, Remahl S, Persson H, Bjartmar C (1993) Myelinated nerve fibres in the CNS. Prog Neurobiol 40:319–384PubMedGoogle Scholar
  299. 299.
    Halter JA, Clark JW Jr. (1993) The influence of nodal constriction on conduction velocity in myelinated nerve fibers. Neuroreport 4:89–92PubMedGoogle Scholar
  300. 300.
    Zimmermann H (1996) Accumulation of synaptic vesicle proteins and cytoskeletal specializations at the peripheral node of Ranvier. Microsc Res Tech 34:462–473PubMedGoogle Scholar
  301. 301.
    Zimmermann H, Vogt M (1989) Membrane proteins of synaptic vesicles and cytoskeletal specializations at the node of Ranvier in electric ray and rat. Cell Tissue Res 258:617–629PubMedGoogle Scholar
  302. 302.
    Weiss P, Hiscoe H (1948) Experiments in the mechanism of nerve growth. J Exp Zool 107:315–395PubMedGoogle Scholar
  303. 303.
    Droz B, Leblond CP (1962) Migration of proteins along the axons of the sciatic nerve. Science 137:1047–1048PubMedGoogle Scholar
  304. 304.
    Lasek RJ (1967) Bidirectional transport of radioactively labelled axoplasmic components. Nature 216:1212–1214PubMedGoogle Scholar
  305. 305.
    Lasek RJ (1968) Axoplasmic transport of labeled proteins in rat ventral motoneurons. Exp Neurol 21:41–51PubMedGoogle Scholar
  306. 306.
    Grafstein B, Forman DS (1980) Intracellular transport in neurons. Physiol Rev 60:1167–1283PubMedGoogle Scholar
  307. 307.
    Dahlstrom A, Haggendal J, Heiwall PO, Larsson PA, Saunders NR (1974) Intra-axonal transport of neurotransmitters in mammalian neurons. Symp Soc Exp Biol 229–247Google Scholar
  308. 308.
    Lombet A, Laduron P, Mourre C, Jacomet Y, Lazdunski M (1985) Axonal transport of the voltage-dependent Na+ channel protein identified by its tetrodotoxin binding site in rat sciatic nerves. Brain Res 345:153–158PubMedGoogle Scholar
  309. 309.
    Hollenbeck PJ (1996) The pattern and mechanism of mitochondrial transport in axons. Front Biosci 1:d91–d102PubMedGoogle Scholar
  310. 310.
    Black MM, Lasek RJ (1980) Slow components of axonal transport: two cytoskeletal networks. J Cell Biol 86:616–623PubMedGoogle Scholar
  311. 311.
    Brady ST (1985) A novel brain ATPase with properties expected for the fast axonal transport motor. Nature 317:73–75PubMedGoogle Scholar
  312. 312.
    Vale RD, Reese TS, Sheetz MP (1985) Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility. Cell 42:39–50PubMedGoogle Scholar
  313. 313.
    Roy S, Coffee P, Smith G, Liem RK, Brady ST, Black MM (2000) Neurofilaments are transported rapidly but intermittently in axons: implications for slow axonal transport. J Neurosci 20:6849–6861PubMedGoogle Scholar
  314. 314.
    Wang L, Ho CL, Sun D, Liem RK, Brown A (2000) Rapid movement of axonal neurofilaments interrupted by prolonged pauses. Nat Cell Biol 2:137–141PubMedGoogle Scholar
  315. 315.
    Trivedi N, Jung P, Brown A (2007) Neurofilaments switch between distinct mobile and stationary states during their transport along axons. J Neurosci 27:507–516PubMedGoogle Scholar
  316. 316.
    Prahlad V, Helfand BT, Langford GM, Vale RD, Goldman RD (2000) Fast transport of neurofilament protein along microtubules in squid axoplasm. J Cell Sci 113(Pt 22):3939–3946PubMedGoogle Scholar
  317. 317.
    Jung C, Lee S, Ortiz D, Zhu Q, Julien JP, Shea TB (2005) The high and middle molecular weight neurofilament subunits regulate the association of neurofilaments with kinesin: inhibition by phosphorylation of the high molecular weight subunit. Brain Res Mol Brain Res 141:151–155PubMedGoogle Scholar
  318. 318.
    LaMonte BH, Wallace KE, Holloway BA, Shelly SS, Ascano J, Tokito M, Van Winkle T, Howland DS, Holzbaur EL (2002) Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron 34:715–727PubMedGoogle Scholar
  319. 319.
    Xia CH, Roberts EA, Her LS, Liu X, Williams DS, Cleveland DW, Goldstein LS (2003) Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A. J Cell Biol 161:55–66PubMedGoogle Scholar
  320. 320.
    Baas PW, Brown A (1997) Slow axonal transport: the polymer transport model. Trends Cell Biol 7:380–384PubMedGoogle Scholar
  321. 321.
    Hirokawa N, Funakoshi ST, Takeda S (1997) Slow axonal transport: the subunit transport model. Trends Cell Biol 7:384–388PubMedGoogle Scholar
  322. 322.
    Lasek RJ, Garner JA, Brady ST (1984) Axonal transport of the cytoplasmic matrix. J Cell Biol 99:212s–221sPubMedGoogle Scholar
  323. 323.
    Okabe S, Miyasaka H, Hirokawa N (1993) Dynamics of the neuronal intermediate filaments. J Cell Biol 121:375–386PubMedGoogle Scholar
  324. 324.
    Terada S, Nakata T, Peterson AC, Hirokawa N (1996) Visualization of slow axonal transport in vivo. Science 273:784–788PubMedGoogle Scholar
  325. 325.
    Popov S, Poo MM (1992) Diffusional transport of macromolecules in developing nerve processes. J Neurosci 12:77–85PubMedGoogle Scholar
  326. 326.
    Yan Y, Brown A (2005) Neurofilament polymer transport in axons. J Neurosci 25:7014–7021PubMedGoogle Scholar
  327. 327.
    Yan Y, Jensen K, Brown A (2007) The polypeptide composition of moving and stationary neurofilaments in cultured sympathetic neurons. Cell Motil Cytoskeleton 64:299–309PubMedGoogle Scholar
  328. 328.
    Yuan A, Rao MV, Kumar A, Julien JP, Nixon RA (2003) Neurofilament transport in vivo minimally requires hetero-oligomer formation. J Neurosci 23:9452–9458PubMedGoogle Scholar
  329. 329.
    Hoffman PN, Lasek RJ, Griffin JW, Price DL (1983) Slowing of the axonal transport of neurofilament proteins during development. J Neurosci 3:1694–1700PubMedGoogle Scholar
  330. 330.
    Yuan A, Nixon RA, Rao MV (2006) Deleting the phosphorylated tail domain of the neurofilament heavy subunit does not alter neurofilament transport rate in vivo. Neurosci Lett 393:264–268PubMedGoogle Scholar
  331. 331.
    Brown A, Wang L, Jung P (2005) Stochastic simulation of neurofilament transport in axons: the “stop-and-go” hypothesis. Mol Biol Cell 16:4243–4255PubMedGoogle Scholar
  332. 332.
    Carpenter S (1968) Proximal axonal enlargement in motor neuron disease. Neurology 18:841–851PubMedGoogle Scholar
  333. 333.
    Averback P (1981) Unusual particles in motor neuron disease. Arch Pathol Lab Med 105:490–493PubMedGoogle Scholar
  334. 334.
    Delisle MB, Carpenter S (1984) Neurofibrillary axonal swellings and amyotrophic lateral sclerosis. J Neurol Sci 63:241–250PubMedGoogle Scholar
  335. 335.
    Hirano A, Donnenfeld H, Sasaki S, Nakano I (1984) Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 43:461–470PubMedGoogle Scholar
  336. 336.
    Munoz DG, Greene C, Perl DP, Selkoe DJ (1988) Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral sclerosis patients. J Neuropathol Exp Neurol 47:9–18PubMedGoogle Scholar
  337. 337.
    Murayama S, Bouldin TW, Suzuki K (1992) Immunocytochemical and ultrastructural studies of upper motor neurons in amyotrophic lateral sclerosis. Acta Neuropathol 83:518–524PubMedGoogle Scholar
  338. 338.
    Xu Z, Cork LC, Griffin JW, Cleveland DW (1993) Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell 73:23–33PubMedGoogle Scholar
  339. 339.
    Bergeron C, Beric-Maskarel K, Muntasser S, Weyer L, Somerville MJ, Percy ME (1994) Neurofilament light and polyadenylated mRNA levels are decreased in amyotrophic lateral sclerosis motor neurons. J Neuropathol Exp Neurol 53:221–230PubMedGoogle Scholar
  340. 340.
    Wong NK, He BP, Strong MJ (2000) Characterization of neuronal intermediate filament protein expression in cervical spinal motor neurons in sporadic amyotrophic lateral sclerosis (ALS). J Neuropathol Exp Neurol 59:972–982PubMedGoogle Scholar
  341. 341.
    Lee MK, Marszalek JR, Cleveland DW (1994) A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease. Neuron 13:975–988PubMedGoogle Scholar
  342. 342.
    Figlewicz DA, Krizus A, Martinoli MG, Meininger V, Dib M, Rouleau GA, Julien JP (1994) Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Genet 3:1757–1761PubMedGoogle Scholar
  343. 343.
    Tomkins J, Usher P, Slade JY, Ince PG, Curtis A, Bushby K, Shaw PJ (1998) Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). Neuroreport 9:3967–3970PubMedGoogle Scholar
  344. 344.
    Al-Chalabi A, Andersen PM, Nilsson P, Chioza B, Andersson JL, Russ C, Shaw CE, Powell JF, Leigh PN (1999) Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum Mol Genet 8:157–164PubMedGoogle Scholar
  345. 345.
    Rooke K, Figlewicz DA, Han FY, Rouleau GA (1996) Analysis of the KSP repeat of the neurofilament heavy subunit in familiar amyotrophic lateral sclerosis. Neurology 46:789–790PubMedGoogle Scholar
  346. 346.
    Vechio JD, Bruijn LI, Xu Z, Brown RH Jr., Cleveland DW (1996) Sequence variants in human neurofilament proteins: absence of linkage to familial amyotrophic lateral sclerosis. Ann Neurol 40:603–610PubMedGoogle Scholar
  347. 347.
    Tu PH, Raju P, Robinson KA, Gurney ME, Trojanowski JQ, Lee VM (1996) Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. Proc Natl Acad Sci U S A 93:3155–3160PubMedGoogle Scholar
  348. 348.
    Borchelt DR, Wong PC, Becher MW, Pardo CA, Lee MK, Xu ZS, Thinakaran G, Jenkins NA, Copeland NG, Sisodia SS, Cleveland DW, Price DL, Hoffman PN (1998) Axonal transport of mutant superoxide dismutase 1 and focal axonal abnormalities in the proximal axons of transgenic mice. Neurobiol Dis 5:27–35PubMedGoogle Scholar
  349. 349.
    Williamson TL, Cleveland DW (1999) Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat Neurosci 2:50–56PubMedGoogle Scholar
  350. 350.
    Zhang B, Tu P, Abtahian F, Trojanowski JQ, Lee VM (1997) Neurofilaments and orthograde transport are reduced in ventral root axons of transgenic mice that express human SOD1 with a G93A mutation. J Cell Biol 139:1307–1315PubMedGoogle Scholar
  351. 351.
    Williamson TL, Bruijn LI, Zhu Q, Anderson KL, Anderson SD, Julien JP, Cleveland DW (1998) Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant. Proc Natl Acad Sci U S A 95:9631–9636PubMedGoogle Scholar
  352. 352.
    Kong J, Xu Z (2000) Overexpression of neurofilament subunit NF-L and NF-H extends survival of a mouse model for amyotrophic lateral sclerosis. Neurosci Lett 281:72–74PubMedGoogle Scholar
  353. 353.
    Couillard-Despres S, Zhu Q, Wong PC, Price DL, Cleveland DW, Julien JP (1998) Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase. Proc Natl Acad Sci U S A 95:9626–9630PubMedGoogle Scholar
  354. 354.
    Roy J, Minotti S, Dong L, Figlewicz DA, Durham HD (1998) Glutamate potentiates the toxicity of mutant Cu/Zn-superoxide dismutase in motor neurons by postsynaptic calcium-dependent mechanisms. J Neurosci 18:9673–9684PubMedGoogle Scholar
  355. 355.
    Ehlers MD, Fung ET, O’Brien RJ, Huganir RL (1998) Splice variant-specific interaction of the NMDA receptor subunit NR1 with neuronal intermediate filaments. J Neurosci 18:720–730PubMedGoogle Scholar
  356. 356.
    Nguyen MD, Lariviere RC, Julien JP (2001) Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions. Neuron 30:135–147PubMedGoogle Scholar
  357. 357.
    Manetto V, Sternberger NH, Perry G, Sternberger LA, Gambetti P (1988) Phosphorylation of neurofilaments is altered in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 47:642–653PubMedGoogle Scholar
  358. 358.
    Morrison BM, Gordon JW, Ripps ME, Morrison JH (1996) Quantitative immunocytochemical analysis of the spinal cord in G86R superoxide dismutase transgenic mice: neurochemical correlates of selective vulnerability. J Comp Neurol 373:619–631PubMedGoogle Scholar
  359. 359.
    Lobsiger CS, Garcia ML, Ward CM, Cleveland DW (2005) Altered axonal architecture by removal of the heavily phosphorylated neurofilament tail domains strongly slows superoxide dismutase 1 mutant-mediated ALS. Proc Natl Acad Sci U S A 102:10351–10356PubMedGoogle Scholar
  360. 360.
    Vande Velde C, Garcia ML, Yin X, Trapp BD, Cleveland DW (2004) The neuroprotective factor Wlds does not attenuate mutant SOD1-mediated motor neuron disease. Neuromolecular Med 5:193–203PubMedGoogle Scholar
  361. 361.
    Migheli A, Pezzulo T, Attanasio A, Schiffer D (1993) Peripherin immunoreactive structures in amyotrophic lateral sclerosis. Lab Invest 68:185–191PubMedGoogle Scholar
  362. 362.
    Beaulieu JM, Nguyen MD, Julien JP (1999) Late onset of motor neurons in mice overexpressing wild-type peripherin. J Cell Biol 147:531–544PubMedGoogle Scholar
  363. 363.
    Beaulieu JM, Jacomy H, Julien JP (2000) Formation of intermediate filament protein aggregates with disparate effects in two transgenic mouse models lacking the neurofilament light subunit. J Neurosci 20:5321–5328PubMedGoogle Scholar
  364. 364.
    Robertson J, Beaulieu JM, Doroudchi MM, Durham HD, Julien JP, Mushynski WE (2001) Apoptotic death of neurons exhibiting peripherin aggregates is mediated by the proinflammatory cytokine tumor necrosis factor-alpha. J Cell Biol 155:217–226PubMedGoogle Scholar
  365. 365.
    Beaulieu JM, Julien JP (2003) Peripherin-mediated death of motor neurons rescued by overexpression of neurofilament NF-H proteins. J Neurochem 85:248–256PubMedGoogle Scholar
  366. 366.
    Ishii T, Haga S, Tokutake S (1979) Presence of neurofilament protein in Alzheimer’s neurofibrillary tangles (ANT). An immunofluorescent study. Acta Neuropathol 48:105–112PubMedGoogle Scholar
  367. 367.
    Nukina N, Kosik KS, Selkoe DJ (1987) Recognition of Alzheimer paired helical filaments by monoclonal neurofilament antibodies is due to cross-reaction with tau protein. Proc Natl Acad Sci U S A 84:3415–3419PubMedGoogle Scholar
  368. 368.
    Schmidt ML, Lee VM, Trojanowski JQ (1990) Relative abundance of tau and neurofilament epitopes in hippocampal neurofibrillary tangles. Am J Pathol 136:1069–1075PubMedGoogle Scholar
  369. 369.
    Selkoe DJ, Ihara Y, Salazar FJ (1982) Alzheimer’s disease: insolubility of partially purified paired helical filaments in sodium dodecyl sulfate and urea. Science 215:1243–1245PubMedGoogle Scholar
  370. 370.
    Sternberger NH, Sternberger LA, Ulrich J (1985) Aberrant neurofilament phosphorylation in Alzheimer disease. Proc Natl Acad Sci U S A 82:4274–4276PubMedGoogle Scholar
  371. 371.
    Lee VM, Otvos L Jr., Schmidt ML, Trojanowski JQ (1988) Alzheimer disease tangles share immunological similarities with multiphosphorylation repeats in the two large neurofilament proteins. Proc Natl Acad Sci U S A 85:7384–7388PubMedGoogle Scholar
  372. 372.
    Wang J, Tung YC, Wang Y, Li XT, Iqbal K, Grundke-Iqbal I (2001) Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer disease brain and in okadaic acid-treated SY5Y cells. FEBS Lett 507:81–87PubMedGoogle Scholar
  373. 373.
    Gong CX, Shaikh S, Wang JZ, Zaidi T, Grundke-Iqbal I, Iqbal K (1995) Phosphatase activity toward abnormally phosphorylated tau: decrease in Alzheimer disease brain. J Neurochem 65:732–738PubMedGoogle Scholar
  374. 374.
    Gong CX, Singh TJ, Grundke-Iqbal I, Iqbal K (1993) Phosphoprotein phosphatase activities in Alzheimer disease brain. J Neurochem 61:921–927PubMedGoogle Scholar
  375. 375.
    Gong CX, Wang JZ, Iqbal K, Grundke-Iqbal I (2003) Inhibition of protein phosphatase 2A induces phosphorylation and accumulation of neurofilaments in metabolically active rat brain slices. Neurosci Lett 340:107–110PubMedGoogle Scholar
  376. 376.
    Liu F, Grundke-Iqbal I, Iqbal K, Gong CX (2005) Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. Eur J Neurosci 22:1942–1950PubMedGoogle Scholar
  377. 377.
    Deng Y, Li B, Liu F, Iqbal K, Grundke-Iqbal I, Brandt R, Gong CX (2008) Regulation between O-GlcNAcylation and phosphorylation of neurofilament-M and their dysregulation in Alzheimer disease. Faseb J 22:138–145PubMedGoogle Scholar
  378. 378.
    Goldman JE, Yen SH, Chiu FC, Peress NS (1983) Lewy bodies of Parkinson’s disease contain neurofilament antigens. Science 221:1082–1084PubMedGoogle Scholar
  379. 379.
    Galloway PG, Mulvihill P, Perry G (1992) Filaments of Lewy bodies contain insoluble cytoskeletal elements. Am J Pathol 140:809–822PubMedGoogle Scholar
  380. 380.
    Iwatsubo T, Yamaguchi H, Fujimuro M, Yokosawa H, Ihara Y, Trojanowski JQ, Lee VM (1996) Purification and characterization of Lewy bodies from the brains of patients with diffuse Lewy body disease. Am J Pathol 148:1517–1529PubMedGoogle Scholar
  381. 381.
    Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc Natl Acad Sci U S A 95:6469–6473PubMedGoogle Scholar
  382. 382.
    Trimmer PA, Borland MK, Keeney PM, Bennett JP Jr., Parker WD Jr. (2004) Parkinson’s disease transgenic mitochondrial cybrids generate Lewy inclusion bodies. J Neurochem 88:800–812PubMedGoogle Scholar
  383. 383.
    Forno LS, Sternberger LA, Sternberger NH, Strefling AM, Swanson K, Eng LF (1986) Reaction of Lewy bodies with antibodies to phosphorylated and non-phosphorylated neurofilaments. Neurosci Lett 64:253–258PubMedGoogle Scholar
  384. 384.
    Pappolla MA (1986) Lewy bodies of Parkinson’s disease. Immune electron microscopic demonstration of neurofilament antigens in constituent filaments. Arch Pathol Lab Med 110:1160–1163PubMedGoogle Scholar
  385. 385.
    Leroy E, Anastasopoulos D, Konitsiotis S, Lavedan C, Polymeropoulos MH (1998) Deletions in the Parkin gene and genetic heterogeneity in a Greek family with early onset Parkinson’s disease. Hum Genet 103:424–427PubMedGoogle Scholar
  386. 386.
    Abbas N, Lucking CB, Ricard S, Durr A, Bonifati V, De Michele G, Bouley S, Vaughan JR, Gasser T, Marconi R, Broussolle E, Brefel-Courbon C, Harhangi BS, Oostra BA, Fabrizio E, Bohme GA, Pradier L, Wood NW, Filla A, Meco G, Denefle P, Agid Y, Brice A (1999) A wide variety of mutations in the Parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson’s Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson’s Disease. Hum Mol Genet 8:567–574PubMedGoogle Scholar
  387. 387.
    Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW, Agid Y, Brice A (2000) Association between early-onset Parkinson’s disease and mutations in the Parkin gene. N Engl J Med 342:1560–1567PubMedGoogle Scholar
  388. 388.
    Lavedan C, Buchholtz S, Nussbaum RL, Albin RL, Polymeropoulos MH (2002) A mutation in the human neurofilament M gene in Parkinson’s disease that suggests a role for the cytoskeleton in neuronal degeneration. Neurosci Lett 322:57–61PubMedGoogle Scholar
  389. 389.
    Perez-Olle R, Lopez-Toledano MA, Liem RK (2004) The G336S variant in the human neurofilament-M gene does not affect its assembly or distribution: importance of the functional analysis of neurofilament variants. J Neuropathol Exp Neurol 63:759–774PubMedGoogle Scholar
  390. 390.
    Han F, Bulman DE, Panisset M, Grimes DA (2005) Neurofilament M gene in a French-Canadian population with Parkinson’s disease. Can J Neurol Sci 32:68–70PubMedGoogle Scholar
  391. 391.
    Kruger R, Fischer C, Schulte T, Strauss KM, Muller T, Woitalla D, Berg D, Hungs M, Gobbele R, Berger K, Epplen JT, Riess O, Schols L (2003) Mutation analysis of the neurofilament M gene in Parkinson’s disease. Neurosci Lett 351:125–129PubMedGoogle Scholar
  392. 392.
    Rahner N, Holzmann C, Kruger R, Schols L, Berger K, Riess O (2002) Neurofilament L gene is not a genetic factor of sporadic and familial Parkinson’s disease. Brain Res 951:82–86PubMedGoogle Scholar
  393. 393.
    Skre H (1974) Genetic and clinical aspects of Charcot-Marie-Tooth’s disease. Clin Genet 6:98–118PubMedCrossRefGoogle Scholar
  394. 394.
    Vogel P, Gabriel M, Goebel HH, Dyck PJ (1985) Hereditary motor sensory neuropathy type II with neurofilament accumulation: new finding or new disorder? Ann Neurol 17:455–461PubMedGoogle Scholar
  395. 395.
    Mersiyanova IV, Perepelov AV, Polyakov AV, Sitnikov VF, Dadali EL, Oparin RB, Petrin AN, Evgrafov OV (2000) A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene. Am J Hum Genet 67:37–46PubMedGoogle Scholar
  396. 396.
    De Jonghe P, Mersivanova I, Nelis E, Del Favero J, Martin JJ, Van Broeckhoven C, Evgrafov O, Timmerman V (2001) Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E. Ann Neurol 49:245–249PubMedGoogle Scholar
  397. 397.
    Brownlees J, Ackerley S, Grierson AJ, Jacobsen NJ, Shea K, Anderton BH, Leigh PN, Shaw CE, Miller CC (2002) Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport. Hum Mol Genet 11:2837–2844PubMedGoogle Scholar
  398. 398.
    Perez-Olle R, Leung CL, Liem RK (2002) Effects of Charcot-Marie-Tooth-linked mutations of the neurofilament light subunit on intermediate filament formation. J Cell Sci 115:4937–4946PubMedGoogle Scholar
  399. 399.
    Perez-Olle R, Lopez-Toledano MA, Goryunov D, Cabrera-Poch N, Stefanis L, Brown K, Liem RK (2005) Mutations in the neurofilament light gene linked to Charcot-Marie-Tooth disease cause defects in transport. J Neurochem 93:861–874PubMedGoogle Scholar
  400. 400.
    Georgiou DM, Zidar J, Korosec M, Middleton LT, Kyriakides T, Christodoulou K (2002) A novel NF-L mutation Pro22Ser is associated with CMT2 in a large Slovenian family. Neurogenetics 4:93–96PubMedGoogle Scholar
  401. 401.
    Fabrizi GM, Cavallaro T, Angiari C, Bertolasi L, Cabrini I, Ferrarini M, Rizzuto N (2004) Giant axon and neurofilament accumulation in Charcot-Marie-Tooth disease type 2E. Neurology 62:1429–1431PubMedGoogle Scholar
  402. 402.
    Yoshihara T, Yamamoto M, Hattori N, Misu K, Mori K, Koike H, Sobue G (2002) Identification of novel sequence variants in the neurofilament-light gene in a Japanese population: analysis of Charcot-Marie-Tooth disease patients and normal individuals. J Peripher Nerv Syst 7:221–224PubMedGoogle Scholar
  403. 403.
    Jordanova A, De Jonghe P, Boerkoel CF, Takashima H, De Vriendt E, Ceuterick C, Martin JJ, Butler IJ, Mancias P, Papasozomenos S, Terespolsky D, Potocki L, Brown CW, Shy M, Rita DA, Tournev I, Kremensky I, Lupski JR, Timmerman V (2003) Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain 126:590–597PubMedGoogle Scholar
  404. 404.
    Fabrizi GM, Cavallaro T, Angiari C, Cabrini I, Taioli F, Malerba G, Bertolasi L, Rizzuto N (2007) Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton. Brain 130:394–403PubMedGoogle Scholar
  405. 405.
    Leung CL, Nagan N, Graham TH, Liem RK (2006) A novel duplication/insertion mutation of NEFL in a patient with Charcot-Marie-Tooth disease. Am J Med Genet A 140:1021–1025PubMedGoogle Scholar
  406. 406.
    Goryunov D, Nightingale A, Bornfleth L, Leung C, Liem RK (2008) Multiple disease-linked myotubularin mutations cause NFL assembly defects in cultured cells and disrupt myotubularin dimerization. J Neurochem 104:1536–1552PubMedGoogle Scholar
  407. 407.
    Sahenk Z (1999) Abnormal Schwann cell-axon interactions in CMT neuropathies. The effects of mutant Schwann cells on the axonal cytoskeleton and regeneration-associated myelination. Ann N Y Acad Sci 883:415–426PubMedGoogle Scholar
  408. 408.
    Bigio EH, Lipton AM, White CL 3rd, Dickson DW, Hirano A (2003) Frontotemporal and motor neurone degeneration with neurofilament inclusion bodies: additional evidence for overlap between FTD and ALS. Neuropathol Appl Neurobiol 29:239–253PubMedGoogle Scholar
  409. 409.
    Cairns NJ, Perry RH, Jaros E, Burn D, McKeith IG, Lowe JS, Holton J, Rossor MN, Skullerud K, Duyckaerts C, Cruz-Sanchez FF, Lantos PL (2003) Patients with a novel neurofilamentopathy: dementia with neurofilament inclusions. Neurosci Lett 341:177–180PubMedGoogle Scholar
  410. 410.
    Josephs KA, Holton JL, Rossor MN, Braendgaard H, Ozawa T, Fox NC, Petersen RC, Pearl GS, Ganguly M, Rosa P, Laursen H, Parisi JE, Waldemar G, Quinn NP, Dickson DW, Revesz T (2003) Neurofilament inclusion body disease: a new proteinopathy? Brain 126:2291–2303PubMedGoogle Scholar
  411. 411.
    Cairns NJ, Grossman M, Arnold SE, Burn DJ, Jaros E, Perry RH, Duyckaerts C, Stankoff B, Pillon B, Skullerud K, Cruz-Sanchez FF, Bigio EH, Mackenzie IR, Gearing M, Juncos JL, Glass JD, Yokoo H, Nakazato Y, Mosaheb S, Thorpe JR, Uryu K, Lee VM, Trojanowski JQ (2004) Clinical and neuropathologic variation in neuronal intermediate filament inclusion disease. Neurology 63:1376–1384PubMedGoogle Scholar
  412. 412.
    Cairns NJ, Zhukareva V, Uryu K, Zhang B, Bigio E, Mackenzie IR, Gearing M, Duyckaerts C, Yokoo H, Nakazato Y, Jaros E, Perry RH, Lee VM, Trojanowski JQ (2004) alpha-internexin is present in the pathological inclusions of neuronal intermediate filament inclusion disease. Am J Pathol 164:2153–2161PubMedGoogle Scholar
  413. 413.
    Uchikado H, Shaw G, Wang DS, Dickson DW (2005) Screening for neurofilament inclusion disease using alpha-internexin immunohistochemistry. Neurology 64:1658–1659PubMedGoogle Scholar
  414. 414.
    Momeni P, Cairns NJ, Perry RH, Bigio EH, Gearing M, Singleton AB, Hardy J (2006) Mutation analysis of patients with neuronal intermediate filament inclusion disease (NIFID). Neurobiol Aging 27:778 e771–778 e776Google Scholar
  415. 415.
    Medori R, Autilio-Gambetti L, Monaco S, Gambetti P (1985) Experimental diabetic neuropathy: impairment of slow transport with changes in axon cross-sectional area. Proc Natl Acad Sci U S A 82:7716–7720PubMedGoogle Scholar
  416. 416.
    Medori R, Jenich H, Autilio-Gambetti L, Gambetti P (1988) Experimental diabetic neuropathy: similar changes of slow axonal transport and axonal size in different animal models. J Neurosci 8:1814–1821PubMedGoogle Scholar
  417. 417.
    Yagihashi S, Kamijo M, Watanabe K (1990) Reduced myelinated fiber size correlates with loss of axonal neurofilaments in peripheral nerve of chronically streptozotocin diabetic rats. Am J Pathol 136:1365–1373PubMedGoogle Scholar
  418. 418.
    Schmidt RE, Beaudet LN, Plurad SB, Dorsey DA (1997) Axonal cytoskeletal pathology in aged and diabetic human sympathetic autonomic ganglia. Brain Res 769:375–383PubMedGoogle Scholar
  419. 419.
    Fernyhough P, Gallagher A, Averill SA, Priestley JV, Hounsom L, Patel J, Tomlinson DR (1999) Aberrant neurofilament phosphorylation in sensory neurons of rats with diabetic neuropathy. Diabetes 48:881–889PubMedGoogle Scholar
  420. 420.
    Scott JN, Clark AW, Zochodne DW (1999) Neurofilament and tubulin gene expression in progressive experimental diabetes: failure of synthesis and export by sensory neurons. Brain 122(Pt 11):2109–2118PubMedGoogle Scholar
  421. 421.
    Berg BO, Rosenberg SH, Asbury AK (1972) Giant axonal neuropathy. Pediatrics 49:894–899PubMedGoogle Scholar
  422. 422.
    Igisu H, Ohta M, Tabira T, Hosokawa S, Goto I (1975) Giant axonal neuropathy. A clinical entity affecting the central as well as the peripheral nervous system. Neurology 25:717–721PubMedGoogle Scholar
  423. 423.
    Bomont P, Cavalier L, Blondeau F, Ben Hamida C, Belal S, Tazir M, Demir E, Topaloglu H, Korinthenberg R, Tuysuz B, Landrieu P, Hentati F, Koenig M (2000) The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nat Genet 26:370–374PubMedGoogle Scholar
  424. 424.
    Pfeiffer J, Schlote W, Bishoff A, Boltshauser E, Müller GS (1977) Generalized giant axonal neuropathy. A filament-forming disease of neuronal, endothelial, glial and Schwann cells in a patient without kinky hair. Acta Neuropathol (Berl.) 40:213–218Google Scholar
  425. 425.
    Asbury AK, Gale MK, Cox SC, Baringer JR, Berg BO (1972) Giant axonal neuropathy—a unique case with segmental neurofilamentous masses. Acta Neuropathol 20:237–247PubMedGoogle Scholar
  426. 426.
    Fois A, Balestri P, Farnetani MA, Berardi R, Mattei R, Laurenzi E, Alessandrini C, Gerli R, Ribuffo A, Calvieri S (1985) Giant axonal neuropathy. Endocrinological and histological studies. Eur J Pediatr 144:274–280PubMedGoogle Scholar
  427. 427.
    Mohri I, Taniike M, Yoshikawa H, Higashiyama M, Itami S, Okada S (1998) A case of giant axonal neuropathy showing focal aggregation and hypophosphorylation of intermediate filaments. Brain Dev 20:594–597PubMedGoogle Scholar
  428. 428.
    Takebe Y, Koide N, Takahashi G (1981) Giant axonal neuropathy: report of two siblings with endocrinological and histological studies. Neuropediatrics 12:392–404PubMedCrossRefGoogle Scholar
  429. 429.
    Treiber-Held S, Budjarjo-Welim H, Reimann D, Richter J, Kretzschmar HA, Hanefeld F (1994) Giant axonal neuropathy: a generalized disorder of intermediate filaments with longitudinal grooves in the hair. Neuropediatrics 25:89–93PubMedGoogle Scholar
  430. 430.
    Yang Y, Allen E, Ding J, Wang W (2007) Giant axonal neuropathy. Cell Mol Life Sci 64:601–609PubMedGoogle Scholar
  431. 431.
    Donaghy M, King RH, Thomas PK, Workman JM (1988) Abnormalities of the axonal cytoskeleton in giant axonal neuropathy. J Neurocytol 17:197–208PubMedGoogle Scholar
  432. 432.
    Monaco S, Autilio-Gambetti L, Zabel D, Gambetti P (1985) Giant axonal neuropathy: acceleration of neurofilament transport in optic axons. Proc Natl Acad Sci U S A 82:920–924PubMedGoogle Scholar
  433. 433.
    Ding J, Allen E, Wang W, Valle A, Wu C, Nardine T, Cui B, Yi J, Taylor A, Jeon NL, Chu S, So Y, Vogel H, Tolwani R, Mobley W, Yang Y (2006) Gene targeting of GAN in mouse causes a toxic accumulation of microtubule-associated protein 8 and impaired retrograde axonal transport. Hum Mol Genet 15:1451–1463PubMedGoogle Scholar
  434. 434.
    Ding J, Liu JJ, Kowal AS, Nardine T, Bhattacharya P, Lee A, Yang Y (2002) Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin. J Cell Biol 158:427–433PubMedGoogle Scholar
  435. 435.
    Wang W, Ding J, Allen E, Zhu P, Zhang L, Vogel H, Yang Y (2005) Gigaxonin interacts with tubulin folding cofactor B and controls its degradation through the ubiquitin-proteasome pathway. Curr Biol 15:2050–2055PubMedGoogle Scholar
  436. 436.
    Allen E, Ding J, Wang W, Pramanik S, Chou J, Yau V, Yang Y (2005) Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival. Nature 438:224–228PubMedGoogle Scholar
  437. 437.
    Griffin JW, Hoffman PN, Clark AW, Carroll PT, Price DL (1978) Slow axonal transport of neurofilament proteins: impairment of beta,beta’-iminodipropionitrile administration. Science 202:633–635PubMedGoogle Scholar
  438. 438.
    Eyer J, McLean WG, Leterrier JF (1989) Effect of a single dose of beta,beta’-iminodipropionitrile in vivo on the properties of neurofilaments in vitro: comparison with the effect of iminodipropionitrile added directly to neurofilaments in vitro. J Neurochem 52:1759–1765PubMedGoogle Scholar
  439. 439.
    Griffin JW, Parhad I, Gold B, Price DL, Hoffman PN, Fahnestock K (1985) Axonal transport of neurofilament proteins in IDPN neurotoxicity. Neurotoxicology 6:43–53PubMedGoogle Scholar
  440. 440.
    Bizzi A, Gambetti P (1986) Phosphorylation of neurofilaments is altered in aluminium intoxication. Acta Neuropathol 71:154–158PubMedGoogle Scholar
  441. 441.
    Shea TB, Balikian P, Beermann ML (1992) Aluminum inhibits neurofilament protein degradation by multiple cytoskeleton-associated proteases. FEBS Lett 307:195–198PubMedGoogle Scholar
  442. 442.
    Shea TB, Beermann ML (1994) Multiple interactions of aluminum with neurofilament subunits: regulation by phosphate-dependent interactions between C-terminal extensions of the high and middle molecular weight subunits. J Neurosci Res 38:160–166PubMedGoogle Scholar
  443. 443.
    Shea TB, Wheeler E, Jung C (1997) Aluminum inhibits neurofilament assembly, cytoskeletal incorporation, and axonal transport. Dynamic nature of aluminum-induced perikaryal neurofilament accumulations as revealed by subunit turnover. Mol Chem Neuropathol 32:17–39PubMedGoogle Scholar
  444. 444.
    Howland RD, Alli P (1986) Altered phosphorylation of rat neuronal cytoskeletal proteins in acrylamide induced neuropathy. Brain Res 363:333–339PubMedGoogle Scholar
  445. 445.
    Gold BG, Price DL, Griffin JW, Rosenfeld J, Hoffman PN, Sternberger NH, Sternberger LA (1988) Neurofilament antigens in acrylamide neuropathy. J Neuropathol Exp Neurol 47:145–157PubMedGoogle Scholar
  446. 446.
    Endo H, Kittur S, Sabri MI (1994) Acrylamide alters neurofilament protein gene expression in rat brain. Neurochem Res 19:815–820PubMedGoogle Scholar
  447. 447.
    Tanii H, Hayashi M, Hashimoto K (1988) Neurofilament degradation in the nervous system of rats intoxicated with acrylamide, related compounds or 2,5-hexanedione. Arch Toxicol 62:70–75PubMedGoogle Scholar
  448. 448.
    Sickles DW, Pearson JK, Beall A, Testino A (1994) Toxic axonal degeneration occurs independent of neurofilament accumulation. J Neurosci Res 39:347–354PubMedGoogle Scholar
  449. 449.
    Takahashi A, Mizutani M, Agr B, Itakura C (1994) Acrylamide-induced neurotoxicity in the central nervous system of Japanese quails. Comparative studies of normal and neurofilament-deficient quails. J Neuropathol Exp Neurol 53:276–283PubMedGoogle Scholar
  450. 450.
    Stone JD, Peterson AP, Eyer J, Oblak TG, Sickles DW (2001) Neurofilaments are nonessential to the pathogenesis of toxicant-induced axonal degeneration. J Neurosci 21:2278–2287PubMedGoogle Scholar
  451. 451.
    Vahidnia A, Romijn F, Tiller M, van der Voet GB, de Wolff FA (2006) Arsenic-induced toxicity: effect on protein composition in sciatic nerve. Hum Exp Toxicol 25:667–674PubMedGoogle Scholar
  452. 452.
    DeFuria J, Shea TB (2007) Arsenic inhibits neurofilament transport and induces perikaryal accumulation of phosphorylated neurofilaments: roles of JNK and GSK-3beta. Brain Res 1181:74–82PubMedGoogle Scholar
  453. 453.
    Lurie DI, Brooks DM, Gray LC (2006) The effect of lead on the avian auditory brainstem. Neurotoxicology 27:108–117PubMedGoogle Scholar
  454. 454.
    Jones LG, Prins J, Park S, Walton JP, Luebke AE, Lurie DI (2008) Lead exposure during development results in increased neurofilament phosphorylation, neuritic beading, and temporal processing deficits within the murine auditory brainstem. J Comp Neurol 506:1003–1017PubMedGoogle Scholar
  455. 455.
    Frappier T, Regnouf F, Pradel LA (1987) Binding of brain spectrin to the 70-kDa neurofilament subunit protein. Eur J Biochem 169:651–657PubMedGoogle Scholar
  456. 456.
    Frappier T, Stetzkowski-Marden F, Pradel LA (1991) Interaction domains of neurofilament light chain and brain spectrin. Biochem J 275(Pt 2):521–527PubMedGoogle Scholar
  457. 457.
    Hao R, MacDonald RG, Ebadi M, Schmit JC, Pfeiffer RF (1997) Stable interaction between G-actin and neurofilament light subunit in dopaminergic neurons. Neurochem Int 31:825–834PubMedGoogle Scholar
  458. 458.
    Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V (2002) The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton. J Biol Chem 277:44180–44186PubMedGoogle Scholar
  459. 459.
    Rao MV, Engle LJ, Mohan PS, Yuan A, Qiu D, Cataldo A, Hassinger L, Jacobsen S, Lee VM, Andreadis A, Julien JP, Bridgman PC, Nixon RA (2002) Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density. J Cell Biol 159:279–290PubMedGoogle Scholar
  460. 460.
    Kim OJ, Ariano MA, Lazzarini RA, Levine MS, Sibley DR (2002) Neurofilament-M interacts with the D1 dopamine receptor to regulate cell surface expression and desensitization. J Neurosci 22:5920–5930PubMedGoogle Scholar
  461. 461.
    Dubois M, Strazielle C, Julien JP, Lalonde R (2005) Mice with the deleted neurofilament of low molecular weight (Nefl) gene: 2. Effects on motor functions and spatial orientation. J Neurosci Res 80:751–758PubMedGoogle Scholar
  462. 462.
    Elder GA, Friedrich VL Jr., Margita A, Lazzarini RA (1999) Age-related atrophy of motor axons in mice deficient in the mid-sized neurofilament subunit. J Cell Biol 146:181–192PubMedGoogle Scholar
  463. 463.
    Elder GA, Friedrich VL Jr., Pereira D, Tu PH, Zhang B, Lee VM, Lazzarini RA (1999) Mice with disrupted midsized and heavy neurofilament genes lack axonal neurofilaments but have unaltered numbers of axonal microtubules. J Neurosci Res 57:23–32PubMedGoogle Scholar
  464. 464.
    Julien JP, Tretjakoff I, Beaudet L, Peterson A (1987) Expression and assembly of a human neurofilament protein in transgenic mice provide a novel neuronal marking system. Genes Dev 1:1085–1095PubMedGoogle Scholar
  465. 465.
    Beaudet L, Cote F, Houle D, Julien JP (1993) Different posttranscriptional controls for the human neurofilament light and heavy genes in transgenic mice. Brain Res Mol Brain Res 18:23–31PubMedGoogle Scholar
  466. 466.
    Ma D, Descarries L, Julien JP, Doucet G (1995) Abnormal perikaryal accumulation of neurofilament light protein in the brain of mice transgenic for the human protein: sequence of postnatal development. Neuroscience 68:135–149PubMedGoogle Scholar
  467. 467.
    Ma D, Descarries L, Micheva KD, Lepage Y, Julien JP, Doucet G (1999) Severe neuronal losses with age in the parietal cortex and ventrobasal thalamus of mice transgenic for the human NF-L neurofilament protein. J Comp Neurol 406:433–448PubMedGoogle Scholar
  468. 468.
    Mathieu JF, Ma D, Descarries L, Vallee A, Parent A, Julien JP, Doucet G (1995) CNS distribution and overexpression of neurofilament light proteins (NF-L) in mice transgenic for the human NF-L: aberrant accumulation in thalamic perikarya. Exp Neurol 132:134–146PubMedGoogle Scholar
  469. 469.
    Lee VM, Elder GA, Chen LC, Liang Z, Snyder SE, Friedrich VL Jr., Lazzarini RA (1992) Expression of human mid-sized neurofilament subunit in transgenic mice. Brain Res Mol Brain Res 15:76–84PubMedGoogle Scholar
  470. 470.
    Vickers JC, Morrison JH, Friedrich VL Jr, Elder GA, Perl DP, Katz RN, Lazzarini RA (1994) Age-associated and cell-type-specific neurofibrillary pathology in transgenic mice expressing the human midsized neurofilament subunit. J Neurosci 14:5603–5612PubMedGoogle Scholar
  471. 471.
    Elder GA, Friedrich VL Jr., Liang Z, Li X, Lazzarini RA (1994) Enhancer trapping by a human mid-sized neurofilament transgene reveals unexpected patterns of neuronal enhancer activity. Brain Res Mol Brain Res 26:177–188PubMedGoogle Scholar
  472. 472.
    Tu PH, Elder G, Lazzarini RA, Nelson D, Trojanowski JQ, Lee VM (1995) Overexpression of the human NFM subunit in transgenic mice modifies the level of endogenous NFL and the phosphorylation state of NFH subunits. J Cell Biol 129:1629–1640PubMedGoogle Scholar
  473. 473.
    Gama Sosa MA, Friedrich VL Jr, DeGasperi R, Kelley K, Wen PH, Senturk E, Lazzarini RA, Elder GA (2003) Human midsized neurofilament subunit induces motor neuron disease in transgenic mice. Exp Neurol 184:408–419PubMedGoogle Scholar
  474. 474.
    Collard JF, Cote F, Julien JP (1995) Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature 375:61–64PubMedGoogle Scholar
  475. 475.
    Xu Z, Tung VW (2000) Overexpression of neurofilament subunit M accelerates axonal transport of neurofilaments. Brain Res 866:326–332PubMedGoogle Scholar
  476. 476.
    Tu PH, Robinson KA, de Snoo F, Eyer J, Peterson A, Lee VM, Trojanowski JQ (1997) Selective degeneration of Purkinje cells with Lewy body-like inclusions in aged NFHLACZ transgenic mice. J Neurosci 17:1064–1074PubMedGoogle Scholar
  477. 477.
    Letournel F, Bocquet A, Perrot R, Dechaume A, Guinut F, Eyer J, Barthelaix A (2006) Neurofilament high molecular weight-green fluorescent protein fusion is normally expressed in neurons and transported in axons: a neuronal marker to investigate the biology of neurofilaments. Neuroscience 137:103–111PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Rodolphe Perrot
    • 2
  • Raphael Berges
    • 1
  • Arnaud Bocquet
    • 3
  • Joel Eyer
    • 1
    Email author
  1. 1.Laboratoire de Neurobiologie and TransgeneseUPRES-EA3143, INSERM IFR132AngersFrance
  2. 2.Centre de Recherche du Centre Hospitalier Universitaire de QuébecDepartment of Anatomy and Physiology of Laval UniversityQuebecCanada
  3. 3.Division des Maladies Cardiovasculaires IICentre de Recherche Pierre FabreCastresFrance

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