Skip to main content
SpringerLink
Log in

Myelination and Regional Domain Differentiation of the Axon

  • Chapter
  • First Online:
Cell Biology of the Axon

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 48))

Abstract

During evolution, as organisms increased in complexity and function, the need for the ensheathment and insulation of axons by glia became vital for faster conductance of action potentials in nerves. Myelination, as the process is termed, facilitates the formation of discrete domains within the axolemma that are enriched in ion channels, and macromolecular complexes consisting of cell adhesion molecules and cytoskeletal regulators. While it is known that glia play a substantial role in the coordination and organization of these domains, the mechanisms involved and signals transduced between the axon and glia, as well as the proteins regulating axo–glial junction formation remain elusive. Emerging evidence has shed light on the processes regulating myelination and domain differentiation, and key molecules have been identified that are required for their assembly and maintenance. This review highlights these recent findings, and relates their significance to domain disorganization as seen in several demyelinating disorders and other neuropathies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abe I, Ochiai N, Ichimura H, Tsujino A, Sun J, Hara Y (2004) Internodes can nearly double in length with gradual elongation of the adult rat sciatic nerve. J Orthop Res 22:571–577

    Article  PubMed  Google Scholar 

  • Alarcon M, Abrahams BS, Stone JL, Duvall JA, Perederiy JV, Bomar JM, Sebat J, Wigler M, Martin CL, Ledbetter DH (2008) Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet 82:150–159

    Article  PubMed  CAS  Google Scholar 

  • Arroyo EJ, Xu YT, Zhou L, Messing A, Peles E, Chiu SY, Scherer SS (1999) Myelinating Schwann cells determine the internodal localization of Kv1.1, Kv1.2, Kvbeta2, and Caspr. J Neurocytol 28:333–347

    Article  PubMed  CAS  Google Scholar 

  • Arroyo EJ, Xu T, Grinspan J, Lambert S, Levinson SR, Brophy PJ, Peles E, Scherer SS (2002) Genetic dysmyelination alters the molecular architecture of the nodal region. J Neurosci 22:1726–1737

    PubMed  CAS  Google Scholar 

  • Baba H, Akita H, Ishibashi T, Inoue, Y, Nakahira K, Ikenaka K (1999) Completion of myelin compaction, but not the attachment of oligodendroglial processes triggers K+ channel clustering. J Neurosci Res 58:752–764

    Article  PubMed  CAS  Google Scholar 

  • Bakkaloglu B, O'Roak BJ, Louvi A, Gupta AR, Abelson JF, Morgan TM, Chawarska K, Klin A, Ercan-Sencicek AG, Stillman AA (2008) Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am J Hum Genet 82:165–173

    Article  PubMed  CAS  Google Scholar 

  • Banerjee S, Bhat MA (2007) Neuron-glial interactions in blood-brain barrier formation. Annu Rev Neurosci 30:235–258

    Article  PubMed  CAS  Google Scholar 

  • Banerjee S, Bhat MA (2008) Glial ensheathment of peripheral axons in Drosophila. J Neurosci Res 86:1189–1198

    Article  PubMed  CAS  Google Scholar 

  • Banerjee S, Pillai AM, Paik R, Li J, Bhat MA (2006a) Axonal ensheathment and septate junction formation in the peripheral nervous system of Drosophila. J Neurosci 26:3319–3329

    Article  CAS  Google Scholar 

  • Banerjee S, Sousa AD, Bhat MA (2006b) Organization and function of septate junctions: an evolutionary perspective. Cell Biochem Biophys 46:65–77

    Article  CAS  Google Scholar 

  • Banerjee S, Bainton RJ, Mayer N, Beckstead R, Bhat MA (2008) Septate junctions are required for ommatidial integrity and blood-eye barrier function in Drosophila. Dev Biol 317:585–599

    Article  PubMed  CAS  Google Scholar 

  • Baumgartner S, Littleton JT, Broadie K, Bhat MA, Harbecke R, Lengyel JA Chiquet- Ehrismann R, Prokop A, Bellen HJ (1996) A Drosophila neurexin is required for septate junction and blood-nerve barrier formation and function. Cell 87:1059–1068

    Article  PubMed  CAS  Google Scholar 

  • Bellen HJ, Lu Y, Beckstead R, Bhat MA (1998) Neurexin IV, caspr and paranodin–novel members of the neurexin family: encounters of axons and glia. Trends Neurosci 21:444–449

    Article  PubMed  CAS  Google Scholar 

  • Bennett V, Lambert S (1999) Physiological roles of axonal ankyrins in survival of premyelinated axons and localization of voltage-gated sodium channels. J Neurocytol 28:303–318

    Article  PubMed  CAS  Google Scholar 

  • Berger P, Niemann A, Suter U (2006) Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease). Glia 54:243–257

    Article  PubMed  Google Scholar 

  • Berghs S, Aggujaro D, Dirkx R Jr, Maksimova E, Stabach P, Hermel JM Zhang JP Philbrick W, Slepnev V, Ort T (2000) βIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system. J Cell Biol 151:985–1002

    Article  PubMed  CAS  Google Scholar 

  • Bhat MA (2003) Molecular organization of axo-glial junctions. Curr Opin Neurobiol 13:552–559

    Article  PubMed  CAS  Google Scholar 

  • Bhat MA, Rios JC, Lu Y, Garcia-Fresco GP, Ching W, St Martin M, Li J, Einheber, S, Chesler M, Rosenbluth J (2001) Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/Paranodin. Neuron 30:369–383

    Article  PubMed  CAS  Google Scholar 

  • Black JA, Waxman SG (1988) The perinodal astrocyte. Glia 1:169–183

    Article  PubMed  CAS  Google Scholar 

  • Boiko T, Rasband MN, Levinson SR, Caldwell JH, Mandel G, Trimmer JS, Matthews G (2001) Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. Neuron 30:91–104

    Article  PubMed  CAS  Google Scholar 

  • Bonnon C, Goutebroze L, Denisenko-Nehrbass N, Girault JA, Faivre-Sarrailh C (2003) The paranodal complex of F3/contactin and caspr/paranodin traffics to the cell surface via a non-conventional pathway. J Biol Chem 278:48339–48347

    Article  PubMed  CAS  Google Scholar 

  • Bouzidi M, Tricaud N, Giraud P, Kordeli E, Caillol G, Deleuze C, Couraud F and Alcaraz, G. (2002) Interaction of the Nav1.2a subunit of the voltage-dependent sodium channel with nodal ankyrinG. In vitro mapping of the interacting domains and association in synaptosomes. J Biol Chem 277:28996–29004

    CAS  Google Scholar 

  • 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 30:385–397

    Article  PubMed  CAS  Google Scholar 

  • Brummendorf T, Rathjen FG (1996) Structure/function relationships of axon-associated adhesion receptors of the immunoglobulin superfamily. Curr Opin Neurobiol 6:584–593

    Article  PubMed  CAS  Google Scholar 

  • Carlson SD, Juang JL, Hilgers SL, Garment MB (2000) Blood barriers of the insect. Annu Rev Entomol 45:151–174

    Article  PubMed  CAS  Google Scholar 

  • Chan JR, Jolicoeur C, Yamauchi J, Elliott J, Fawcett JP, Ng BK, Cayouette M (2006) The polarity protein Par-3 directly interacts with p75NTR to regulate myelination. Science 314:832–836

    Article  PubMed  CAS  Google Scholar 

  • Charles P, Tait S, Faivre-Sarrailh C, Barbin G, Gunn-Moore F, Denisenko-Nehrbass N, Guennoc AM, Girault JA, Brophy PJ, Lubetzki, C (2002) Neurofascin is a glial receptor for the paranodin/Caspr-contactin axonal complex at the axoglial junction. Curr Biol 12:217–220

    Article  PubMed  CAS  Google Scholar 

  • Chernousov MA, Carey DJ (2000) Schwann cell extracellular matrix molecules and their receptors. Histol Histopathol 15:593–601

    PubMed  CAS  Google Scholar 

  • Chiu SY, Zhou L, Zhang CL, Messing A (1999) Analysis of potassium channel functions In mammalian axons by gene knockouts. J Neurocytol 28:349–364

    Article  PubMed  CAS  Google Scholar 

  • Coetzee T, Fujita N, Dupree J, Shi R, Blight A, Suzuki K, Popko B (1996) Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability. Cell 86:209–219

    Article  PubMed  CAS  Google Scholar 

  • Collinson JM, Marshall D, Gillespie CS, Brophy PJ (1998) Transient expression of neurofascin by oligodendrocytes at the onset of myelinogenesis: implications for mechanisms of axon-glial interaction. Glia 23:11–23

    Article  PubMed  CAS  Google Scholar 

  • Coman I, Aigrot MS, Seilhean D, Reynolds R, Girault JA, Zalc B, Lubetzki C (2006) Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis. Brain 129:3186–3195

    Article  PubMed  CAS  Google Scholar 

  • Court FA, Wrabetz L., Feltri ML (2006) Basal lamina: Schwann cells wrap to the rhythm of space-time. Curr Opin Neurobiol 16:501–507

    Article  PubMed  CAS  Google Scholar 

  • Custer AW, Kazarinova-Noyes K, Sakurai T, Xu X, Simon W Grumet M, Shrager P (2003) The role of the ankyrin-binding protein NrCAM in node of Ranvier formation. J Neurosci 23:10032–10039

    PubMed  CAS  Google Scholar 

  • Davis JQ, Bennett V (1993) Ankyrin-binding activity of nervous system cell adhesion molecules expressed in adult brain. J Cell Sci Suppl 17:109–117

    PubMed  CAS  Google Scholar 

  • Davis JQ, Lambert S, Bennett V (1996) Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain-) and NrCAM at nodal axon segments. J Cell Biol 135:1355–1367

    Article  PubMed  CAS  Google Scholar 

  • Denisenko-Nehrbass N, Faivre-Sarrailh C, Goutebroze, L, Girault JA (2002) A molecular view on paranodal junctions of myelinated fibers. J Physiol 96:99–103

    CAS  Google Scholar 

  • Denisenko-Nehrbass N, Goutebroze L, Galvez T, Bonnon C, Stankoff B, Ezan P Giovannini M, Faivre-Sarrailh C, Girault JA (2003a) Association of Caspr/paranodin with tumour suppressor schwannomin/merlin and 1 integrin in the central nervous system. J Neurochem 84:209–221

    Article  CAS  Google Scholar 

  • Denisenko-Nehrbass N, Oguievetskaia K, Goutebroze L, Galvez T, Yamakawa H, Ohara O, Carnaud M, Girault JA (2003b) Protein 4.1B associates with both Caspr/paranodin and Caspr2 at paranodes and juxtaparanodes of myelinated fibres. Eur J Neurosci 17:411–416

    Article  Google Scholar 

  • Doerflinger NH, Macklin WB, Popko B (2003) Inducible site-specific recombination in myelinating cells. Genesis 35:63–72

    Article  PubMed  CAS  Google Scholar 

  • Dupree JL, Coetzee T, Suzuki K, Popko B (1998) Myelin abnormalities in mice deficient in galactocerebroside and sulfatide. J Neurocytol 27:649–659

    Article  PubMed  CAS  Google Scholar 

  • Dupree JL, Girault JA, Popko B (1999) Axo-glial interactions regulate the localization of axonal paranodal proteins. J Cell Biol 147:1145–1152

    Article  PubMed  CAS  Google Scholar 

  • Einheber S, Zanazzi G, Ching W, Scherer S, Milner TA, Peles E, Salzer JL (1997) The axonal membrane protein Caspr, a homologue of neurexin IV, is a component of the septate-like paranodal junctions that assemble during myelination. J Cell Biol 139:1495–1506

    Article  PubMed  CAS  Google Scholar 

  • Eshed Y, Feinberg K, Poliak S, Sabanay H, Sarig-Nadir O, Spiegel I, Bermingham JR Jr, Peles E (2005) Gliomedin mediates Schwann cell-axon interaction and the molecular assembly of the nodes of Ranvier. Neuron 47:215–229

    Article  PubMed  CAS  Google Scholar 

  • Eshed Y, Feinberg K, Carey DJ, Peles E (2007) Secreted gliomedin is a perinodal matrix component of peripheral nerves. J Cell Biol 177:551–562

    Article  PubMed  CAS  Google Scholar 

  • Fabrizi GM, Ferrarini M, Cavallaro T, Cabrini I, Cerini R, Bertolasi L, Rizzuto N (2007) Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease. Neurol 69:291–295

    Article  CAS  Google Scholar 

  • Faivre-Sarrailh C, Gauthier F, Denisenko-Nehrbass N, Le Bivic A, Rougon G, Girault JA (2000) The glycosylphosphatidyl inositol-anchored adhesion molecule F3/contactin is required for surface transport of paranodin/contactin-associated protein (caspr). J Cell Biol 149:491–502

    Article  PubMed  CAS  Google Scholar 

  • Faivre-Sarrailh C, Banerjee S, Li J, Hortsch M, Laval M, Bhat MA (2004) Drosophila contactin, a homolog of vertebrate contactin, is required for septate junction organization and paracellular barrier function. Development 131:4931–4942

    Article  PubMed  CAS  Google Scholar 

  • Falk J, Bonnon C, Girault JA, Faivre-Sarrailh C (2002) F3/contactin, a neuronal cell adhesion molecule implicated in axogenesis and myelination. Biol Cell 94:327–334

    Article  PubMed  CAS  Google Scholar 

  • Furley AJ, Morton SB, Manalo D, Karagogeos D, Dodd J, Jessell TM (1990) The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity. Cell 61:157–170

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Fresco GP, Sousa AD, Pillai AM, Moy SS, Crawley JN, Tessarollo L, Dupree JL, Bhat MA (2006) Disruption of axo-glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons. Proc Natl Acad Sci U S A 103:5137–5142

    Article  PubMed  CAS  Google Scholar 

  • Garver TD, Ren Q, Tuvia S, Bennett V (1997) Tyrosine phosphorylation at a site highly conserved in the L1 family of cell adhesion molecules abolishes ankyrin binding and increases lateral mobility of neurofascin. J Cell Biol 137:703–714

    Article  PubMed  CAS  Google Scholar 

  • Gatto CL. Walker BJ, Lambert S (2003) Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient formation of nodes of Ranvier. J Cell Biol 162:489–498

    Article  PubMed  CAS  Google Scholar 

  • Gollan L, Sabanay H, Poliak S, Berglund EO, Ranscht B, Peles E (2002) Retention of a cell adhesion complex at the paranodal junction requires the cytoplasmic region of Caspr. J Cell Biol 157:1247–1256

    Article  PubMed  CAS  Google Scholar 

  • Gollan L, Salomon D, Salzer JL, Peles E (2003) Caspr regulates the processing of contactin and inhibits its binding to neurofascin. J Cell Biol 163:1213–1218

    Article  PubMed  CAS  Google Scholar 

  • Goutebroze L, Carnaud M, Denisenko N, Boutterin MC, Girault JA (2003) Syndecan-3 and syndecan-4 are enriched in Schwann cell perinodal processes. BMC Neurosci 4:29

    Article  PubMed  Google Scholar 

  • Grumet M (1997) Nr-CAM: a cell adhesion molecule with ligand and receptor functions. Cell Tissue Res 290:423–428

    Article  PubMed  CAS  Google Scholar 

  • Gunn-Moore FJ, Hill M, Davey F, Herron LR, Tait S, Sherman D, Brophy PJ (2006) A functional FERM domain binding motif in neurofascin. Mol Cell Neurosci 33:441–446

    Article  PubMed  CAS  Google Scholar 

  • Hassel B, Rathjen FG, Volkmer H (1997) Organization of the neurofascin gene and analysis of developmentally regulated alternative splicing. J Biol Chem 272:28742–28749

    Article  PubMed  CAS  Google Scholar 

  • Hildebrand C, Remahl S, Persson H, Bjartmar C (1993) Myelinated nerve fibres in the CNS. Prog Neurobiol 40:319–384

    Article  Google Scholar 

  • Holm J, Hillenbrand R, Steuber V, Bartsch U, Moos M, Lubbert H, Montag D, Schachner M (1996) Structural features of a close homologue of L1 (CHL1) in the mouse: a new member of the L1 family of neural recognition molecules. Eur J Neurosci 8:1613–1629

    Article  PubMed  CAS  Google Scholar 

  • Honke K, Hirahara Y, Dupree J, Suzuki K, Popko B, Fukushima K, Fukushima J, Nagasawa T, Yoshida N, Wada Y (2002) Paranodal junction formation and spermatogenesis require sulfoglycolipids. Proc Natl Acad Sci U S A 99:4227–4232

    Article  PubMed  CAS  Google Scholar 

  • Hoover KB, Bryant PJ (2000) The genetics of the protein 4.1 family: organizers of the membrane and cytoskeleton. Curr Opin Cell Biol 12:229–234

    Article  PubMed  CAS  Google Scholar 

  • Hoshi T, Suzuki A, Hayashi S, Tohyama K, Hayashi A, Yamaguchi Y, Takeuchi K, Baba, H (2007) Nodal protrusions, increased Schmidt-Lanterman incisures, and paranodal disorganization are characteristic features of sulfatide-deficient peripheral nerves. Glia 55:584–594

    Article  PubMed  Google Scholar 

  • Howell OW, Palser A, Polito A, Melrose S, Zonta B, Scheiermann C, Vora AJ, Brophy PJ, Reynolds R (2006) Disruption of neurofascin localization reveals early changes preceding demyelination and remyelination in multiple sclerosis. Brain 129:3173–3185

    Article  PubMed  CAS  Google Scholar 

  • Ichimura T, Ellisman MH (1991) Three-dimensional fine structure of cytoskeletal- membrane interactions at nodes of Ranvier. J Neurocytol 20:667–681

    Article  PubMed  CAS  Google Scholar 

  • Ishibashi T, Dupree JL Ikenaka K Hirahara Y, Honke K, Peles E, Popko B, Suzuki K, Nishino H, Baba H (2002) A myelin galactolipid, sulfatide, is essential for maintenance of ion channels on myelinated axon but not essential for initial cluster formation. J Neurosci 22:6507–6514

    PubMed  CAS  Google Scholar 

  • Isom LL (2002) The role of sodium channels in cell adhesion. Front Biosci 7:12–23

    Article  PubMed  Google Scholar 

  • Jenkins SM, Bennett V (2001) Ankyrin-G coordinates assembly of the spectrin-based membrane skeleton, voltage-gated sodium channels, and L1 CAMs at Purkinje neuron initial segments. J Cell Biol 155:739–746

    Article  PubMed  CAS  Google Scholar 

  • Jenkins SM, Bennett V (2002) Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion. Proc Natl Acad Sci U S A 99:2303–2308

    Article  PubMed  CAS  Google Scholar 

  • Jessen KR, Mirsky R (2005) The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci 6:671–682

    Article  PubMed  CAS  Google Scholar 

  • Kaplan MR, Meyer-Franke A, Lambert S, Bennett V, Duncan ID, Levinson SR, Barres BA (1997) Induction of sodium channel clustering by oligodendrocytes. Nature 386:724–728

    Article  PubMed  CAS  Google Scholar 

  • Kaplan MR, Cho MH, Ullian EM, Isom LL, Levinson SR, Barres BA (2001) Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier. Neuron 30:105–119

    Article  PubMed  CAS  Google Scholar 

  • Karagogeos D, Morton SB, Casano F, Dodd J, Jessell TM (1991) Developmental expression of the axonal glycoprotein TAG-1: differential regulation by central and peripheral neurons in vitro. Development 112:51–67

    PubMed  CAS  Google Scholar 

  • Kearney JA, Buchner DA, De Haan G, Adamska M, Levin SI, Furay AR, Albin RL, Jones JM, Montal M, Stevens MJ (2002) Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Na(v)1.6). Hum Mol Genet 11:2765–2775

    Article  PubMed  CAS  Google Scholar 

  • Komada M, Soriano P (2002) BetaIV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier. J Cell Biol 156:337-348

    Article  PubMed  CAS  Google Scholar 

  • Kordeli E, Lambert S, Bennett V (1995) AnkyrinG. A new ankyrin gene with neural- specific isoforms localized at the axonal initial segment and node of Ranvier. J Biol Chem 270:2352–2359

    CAS  Google Scholar 

  • Lacas-Gervais S, Guo J, Strenzke N, Scarfone E, Kolpe M, Jahkel M, De Camilli P, Moser T, Rasband MN, Solimena M (2004) BetaIVSigma1 spectrin stabilizes the nodes of Ranvier and axon initial segments. J Cell Biol 166:983–990

    Article  PubMed  CAS  Google Scholar 

  • Lambert S, Davis JQ, Bennett V (1997) Morphogenesis of the node of Ranvier: co- clusters of ankyrin and ankyrin-binding integral proteins define early developmental intermediates. J Neurosci 17:7025–7036

    PubMed  CAS  Google Scholar 

  • Lappe-Siefke C, Goebbels S, Gravel M, Nicksch E, Lee J, Braun PE, Griffiths IR, Nave KA (2003) Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination. Nat Genet 33:366–374

    Article  PubMed  CAS  Google Scholar 

  • Laval M, Bel C, Faivre-Sarrailh C (2008) The lateral mobility of cell adhesion molecules is highly restricted at septate junctions in Drosophila. BMC Cell Biol 9:38

    Article  PubMed  CAS  Google Scholar 

  • Lemaillet G, Walker B, Lambert S (2003) Identification of a conserved ankyrin-binding motif in the family of sodium channel alpha subunits. J Biol Chem 278:27333–27339

    Article  PubMed  CAS  Google Scholar 

  • Lubetzki C, Williams A, Stankoff B (2005) Promoting repair in multiple sclerosis: problems and prospects. Curr Opin Neurol 18:237–244

    Article  PubMed  CAS  Google Scholar 

  • Lustig M, Zanazzi G, Sakurai T, Blanco C, Levinson SR, Lambert S, Grumet M, Salzer JL (2001). Nr-CAM and neurofascin interactions regulate ankyrin G and sodium channel clustering at the node of Ranvier. Curr Biol 11:1864–1869

    Article  PubMed  CAS  Google Scholar 

  • Maier O, van der Heide T, van Dam AM, Baron W, de Vries H, Hoekstra D (2005) Alteration of the extracellular matrix interferes with raft association of neurofascin in oligodendrocytes. Potential significance for multiple sclerosis? Mol Cell Neurosci 28:390–401

    CAS  Google Scholar 

  • Maier O, Baron W, Hoekstra D (2007) Reduced raft-association of NF155 in active MS- lesions is accompanied by the disruption of the paranodal junction. Glia 55:885–895

    Article  PubMed  Google Scholar 

  • Malhotra JD, Koopmann MC, Kazen-Gillespie KA, Fettman N, Hortsch M, Isom LL (2002) Structural requirements for interaction of sodium channel β1 subunits with ankyrin. J Biol Chem 277:26681–26688

    Article  PubMed  CAS  Google Scholar 

  • Marcus J, Popko B (2002) Galactolipids are molecular determinants of myelin development and axo-glial organization. Biochim Biophys Acta 1573:406–413

    Article  PubMed  CAS  Google Scholar 

  • Mathey EK, Derfuss T, Storch, MK, Williams KR, Hales K, Woolley DR, Al-Hayani A, Davies SN, Rasband MN, Olsson T (2007) Neurofascin as a novel target for autoantibody-mediated axonal injury. J Exp Med 204:2363–2372

    Article  PubMed  CAS  Google Scholar 

  • Maurel P, Einheber S, Galinska J, Thaker P, Lam I, Rubin MB, Scherer SS, Murakami Y, Gutmann DH, Salzer JL (2007) Nectin-like proteins mediate axon Schwann cell interactions along the internode and are essential for myelination. J Cell Biol 178:861–874

    Article  PubMed  CAS  Google Scholar 

  • Melendez-Vasquez CV, Rios JC, Zanazzi G, Lambert S, Bretscher A, Salzer JL (2001) Nodes of Ranvier form in association with ezrin-radixin-moesin (ERM)-positive Schwann cell processes. Proc Natl Acad Sci U S A 98:1235–1240

    Article  PubMed  CAS  Google Scholar 

  • Melendez-Vasquez CV, Einheber S, Salzer JL (2004) Rho kinase regulates schwann cell myelination and formation of associated axonal domains. J Neurosci 24:3953–3963

    Article  PubMed  CAS  Google Scholar 

  • Menegoz M, Gaspar P, Le Bert M, Galvez T, Burgaya F, Palfrey C, Ezan P, Arnos F, Girault JA (1997) Paranodin, a glycoprotein of neuronal paranodal membranes. Neuron 19:319–331

    Article  PubMed  CAS  Google Scholar 

  • Mi F, Berkowitz GA (1995) Development of a K+-channel probe and its use for identification of an intracellular plant membrane K+ channel. Proc Natl Acad Sci U S A 92:3386–3390

    Article  PubMed  CAS  Google Scholar 

  • Morell P, Toews AD, Wagner, M, Goodrum JF (1994) Gene expression during tellurium- induced primary demyelination. Neurotoxicology 15:171–180

    PubMed  CAS  Google Scholar 

  • Moscoso LM, Sanes JR (1995) Expression of four immunoglobulin superfamily adhesion molecules (L1, Nr-CAM/Bravo, neurofascin/ABGP, and N-CAM) in the developing mouse spinal cord. J Comp Neurol 352:321–334

    Article  PubMed  CAS  Google Scholar 

  • Nave KA, Sereda MW, Ehrenreich H (2007) Mechanisms of disease: inherited demyelinating neuropathies–from basic to clinical research. Nat Clin Pract Neurol 3:453–464

    Article  PubMed  CAS  Google Scholar 

  • Norton WT, Cammer W (1984) Isolation and characterization of myelin. In: Morell P (ed) Myelin. Plenum, New York, pp 147–195

    Google Scholar 

  • Occhi S, Zambroni D, Del Carro U, Amadio S, Sirkowski EE, Scherer SS, Campbell KP, Moore SA, Chen ZL, Strickland S (2005) Both laminin and Schwann cell dystroglycan are necessary for proper clustering of sodium channels at nodes of Ranvier. J Neurosci 25:9418–9427

    Article  PubMed  CAS  Google Scholar 

  • Ogawa Y, Schafer DP, Horresh I, Bar V, Hales K, Yang Y, Susuki K, Peles E, Stankewich MC, Rasband M (2006). Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton. J Neurosci 26:5230–5239

    Article  PubMed  CAS  Google Scholar 

  • Oguievetskaia K, Cifuentes-Diaz C, Girault JA, Goutebroze L (2005) Cellular contacts in myelinated fibers of the peripheral nervous system. Med Sci 21:162–169

    Google Scholar 

  • Ohara R, Yamakawa H, Nakayama M, Ohara O (2000) Type II brain 4.1 (4.1B/KIAA0987), a member of the protein 4.1 family, is localized to neuronal paranodes. Brain Res Mol Brain Res 85:41–52

    Article  PubMed  CAS  Google Scholar 

  • Ohno S (2001) Intercellular junctions and cellular polarity: the PAR-aPKC complex, a conserved core cassette playing fundamental roles in cell polarity. Curr Opin Cell Biol 13:641–648

    Article  PubMed  CAS  Google Scholar 

  • Park J, Liu B, Chen T, Li H, Hu X, Gao J, Zhu Y, Zhu Q, Qiang B, Yuan J (2008) Disruption of Nectin-like 1 cell adhesion molecule leads to delayed axonal myelination in the CNS. J Neurosci 28:12815–12819

    Article  PubMed  CAS  Google Scholar 

  • Parra M, Gascard P, Walensky LD, Gimm JA, Blackshaw S, Chan N, Takakuwa Y, Berger T, Lee G, Chasis JA (2000) Molecular and functional characterization of protein 4.1B, a novel member of the protein 4.1 family with high level, focal expression in brain. J Biol Chem 275:3247–3255

    Article  PubMed  CAS  Google Scholar 

  • Pedraza L, Huang JK, Colman DR (2001) Organizing principles of the axoglial apparatus. Neuron 30:335–344

    Article  PubMed  CAS  Google Scholar 

  • Peles E, Salzer JL (2000) Molecular domains of myelinated axons. Curr Opin Neurobiol 10:558–565

    Article  PubMed  CAS  Google Scholar 

  • Peles E, Nativ, M, Lustig M, Grumet M, Schilling J, Martinez R, Plowman GD, Schlessinger J (1997) Identification of a novel contactin-associated transmembrane receptor with multiple domains implicated in protein-protein interactions. EMBO J 16:978–988

    Article  PubMed  CAS  Google Scholar 

  • Pillai AM, Garcia-Fresco GP, Sousa AD, Dupree JL, Philpot BD, Bhat MA (2007) No effect of genetic deletion of contactin-associated protein (CASPR) on axonal orientation and synaptic plasticity. J Neurosci Res 85:2318–2331

    Article  PubMed  CAS  Google Scholar 

  • Pillai AM, Thaxton C, Pribisko AL, Cheng J-G, Dupree JL, Bhat MA (2009) Spatio- temporal ablation of myelinating glia-specific neurofascin (nfascnf155) in mice reveals gradual loss of paranodal axo-glial junctions and concomitant disorganization of axonal domains. J Neurosci Res Jan 30. [Epub ahead of print]

    Google Scholar 

  • Pinheiro EM, Montell DJ (2004) Requirement for Par-6 and Bazooka in Drosophila border cell migration. Development 131:5243–5251

    Article  PubMed  CAS  Google Scholar 

  • Poliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer JL, Trimmer JS, Shrager P, Peles E (1999) Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron 24:1037–1047

    Article  PubMed  CAS  Google Scholar 

  • Poliak S, Gollan L, Salomon D, Berglund EO, Ohara R, Ranscht B, Peles E (2001). Localization of Caspr2 in myelinated nerves depends on axon-glia interactions and the generation of barriers along the axon. J Neurosci 21:7568–7575

    PubMed  CAS  Google Scholar 

  • Poliak S, Salomon D, Elhanany H, Sabanay H, Kiernan B, Pevny L, Stewart CL, Xu X, Chiu SY, Shrager P (2003) Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1. J Cell Biol 162:1149–1160

    Article  PubMed  CAS  Google Scholar 

  • Rasband MN, Trimmer JS, Schwarz TL, Levinson SR, Ellisman MH, Schachner M, Shrager P (1998) Potassium channel distribution, clustering, and function in remyelinating rat axons. J Neurosci 18:36–47

    Google Scholar 

  • Rasband MN, Peles E, Trimmer JS, Levinson SR, Lux SE, Shrager P (1999) Dependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS. J Neurosci 19:7516–7528

    Google Scholar 

  • Rasband MN, Park EW, Zhen D, Arbuckle MI, Poliak S, Peles E, Grant SG, Trimmer JS (2002) Clustering of neuronal potassium channels is independent of their interaction with PSD-95. J Cell Biol 159:663–672

    Article  CAS  Google Scholar 

  • Reid RA, Bronson DD, Young KM, Hemperly JJ (1994) Identification and characterization of the human cell adhesion molecule contactin. Brain Res Mol Brain Res 21:1–8

    Article  PubMed  CAS  Google Scholar 

  • Rios JC, Melendez-Vasquez CV, Einheber S, Lustig M, Grumet M, Hemperly J, Peles E, Salzer JL (2000) Contactin-associated protein (Caspr) and contactin form a complex that is targeted to the paranodal junctions during myelination. J Neurosci 20:8354–8364

    PubMed  CAS  Google Scholar 

  • Rodriguez M, Scheithauer B (1994) Ultrastructure of multiple sclerosis. Ultrastruct Pathol 18:3–13

    Article  PubMed  CAS  Google Scholar 

  • Saito F, Moore SA, Barresi R, Henry MD, Messing A, Ross-Barta SE, Cohn RD, Williamson RA, Sluka KA, Sherman DL (2003) Unique role of dystroglycan in peripheral nerve myelination, nodal structure, and sodium channel stabilization. Neuron 38:747–758

    Article  PubMed  CAS  Google Scholar 

  • Salzer JL (2003) Polarized domains of myelinated axons. Neuron 40:297–318

    Article  PubMed  CAS  Google Scholar 

  • Salzer JL, Brophy PJ, Peles E (2008) Molecular domains of myelinated axons in the peripheral nervous system. Glia 56:1532–1540

    Article  PubMed  Google Scholar 

  • Savvaki M, Panagiotaropoulos T, Stamatakis A, Sargiannidou I, Karatzioula P, Watanabe K, Stylianopoulou F, Karagogeos D, Kleopa, KA (2008) Impairment of learning and memory in TAG-1 deficient mice associated with shorter CNS internodes and disrupted juxtaparanodes. Mol Cell Neurosci 39:478–490

    Article  PubMed  CAS  Google Scholar 

  • Schafer DP, Bansal R, Hedstrom KL, Pfeiffer SE, Rasband MN (2004) Does paranode formation and maintenance require partitioning of neurofascin 155 into lipid rafts? J Neurosci 24:3176–3185

    Article  PubMed  CAS  Google Scholar 

  • Sherman DL, Tait S, Melrose S, Johnson R, Zonta B, Court FA, Macklin WB, Meek S, Smith AJ, Cottrell DF (2005) Neurofascins are required to establish axonal domains for saltatory conduction. Neuron 48:737–742

    Article  PubMed  CAS  Google Scholar 

  • Shy ME (2006) Peripheral neuropathies caused by mutations in the myelin protein zero. J Neurol Sci 242:55–66

    Article  PubMed  CAS  Google Scholar 

  • Simons M, Trotter J (2007) Wrapping it up: the cell biology of myelination. Curr Opin Neurobiol 17:533–540

    Article  PubMed  CAS  Google Scholar 

  • Sousa AD, Bhat MA (2007) Cytoskeletal transition at the paranodes: the Achilles' heel of myelinated axons. Neuron Glia Biol 3:169–178

    Article  PubMed  Google Scholar 

  • Spiegel I, Salomon D, Erne B, Schaeren-Wiemers N, Peles E (2002) Caspr3 and caspr4, two novel members of the caspr family are expressed in the nervous system and interact with PDZ domains. Mol Cell Neurosci 20:283–297

    Article  PubMed  CAS  Google Scholar 

  • Sun CX, Robb VA, Gutmann DH (2002) Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation. J Cell Sci 115:3991–4000

    Article  PubMed  CAS  Google Scholar 

  • Tait S, Gunn-Moore F, Collinson JM, Huang J, Lubetzki C, Pedraza L, Sherman DL, Colman DR, Brophy PJ (2000) An oligodendrocyte cell adhesion molecule at the site of assembly of the paranodal axo-glial junction. J Cell Biol 150:657–666

    Article  PubMed  CAS  Google Scholar 

  • Takai Y, Irie K, Shimizu K, Sakisaka T, Ikeda W (2003) Nectins and nectin-like molecules: roles in cell adhesion, migration, and polarization. Cancer Sci 94:655–667

    Article  PubMed  CAS  Google Scholar 

  • Takekuni K, Ikeda W, Fujito T, Morimoto K, Takeuchi M, Monden M, Takai Y (2003) Direct binding of cell polarity protein PAR-3 to cell-cell adhesion molecule nectin at neuroepithelial cells of developing mouse. J Biol Chem 278:5497–5500

    Article  PubMed  CAS  Google Scholar 

  • Tepass U, Tanentzapf G, Ward R, Fehon R (2001) Epithelial cell polarity and cell junctions in Drosophila. Annu Rev Genet 35:747–784

    Article  PubMed  CAS  Google Scholar 

  • Traka M, Dupree JL, Popko B, Karagogeos D (2002) The neuronal adhesion protein TAG-1 is expressed by Schwann cells and oligodendrocytes and is localized to the juxtaparanodal region of myelinated fibers. J Neurosci 22:3016–3024

    PubMed  CAS  Google Scholar 

  • Traka M, Goutebroze, L, Denisenko N, Bessa M, Nifli A, Havaki S, Iwakura Y, Fukamauchi F, Watanabe K, Soliven B (2003) Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers. J Cell Biol 162:1161–1172

    Article  PubMed  CAS  Google Scholar 

  • Trapp BD, Nave KA (2008) Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 31:247–269

    Article  PubMed  CAS  Google Scholar 

  • Tzimourakas A, Giasemi S, Mouratidou M, Karagogeos D (2007) Structure-function analysis of protein complexes involved in the molecular architecture of juxtaparanodal regions of myelinated fibers. Biotechnol J 2:577–583

    Article  PubMed  CAS  Google Scholar 

  • Vernes SC, Newbury DF, Abrahams BS, Winchester L, Nicod J, Groszer M, Alarcon M, Oliver PL, Davies KE, Geschwind DH (2008) A functional genetic link between distinct developmental language disorders. N Engl J Med 359:2337–2345

    Article  PubMed  CAS  Google Scholar 

  • Voas MG, Lyons DA, Naylor SG, Arana N, Rasband MN, Talbot WS (2007) αII-spectrin is essential for assembly of the nodes of Ranvier in myelinated axons. Curr Biol 17:562–568

    Article  PubMed  CAS  Google Scholar 

  • Volkmer H, Hassel B, Wolff JM, Frank R, Rathjen FG (1992) Structure of the axonal surface recognition molecule neurofascin and its relationship to a neural subgroup of the immunoglobulin superfamily. J Cell Biol 118:149–161

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Kunkel DD, Martin TM, Schwartzkroin PA, Tempel BL (1993) Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons. Nature 365:75–79

    Article  PubMed  CAS  Google Scholar 

  • Ward RE, Lamb RS, Fehon, RG (1998) A conserved functional domain of Drosophila coracle is required for localization at the septate junction and has membrane- organizing activity. J Cell Biol 140:1463–1473

    Article  PubMed  CAS  Google Scholar 

  • Waxman SG, Ritchie JM (1993) Molecular dissection of the myelinated axon. Ann Neurol 33:121–136

    Article  PubMed  CAS  Google Scholar 

  • Wolswijk G, Balesar R (2003) Changes in the expression and localization of the paranodal protein Caspr on axons in chronic multiple sclerosis. Brain 126:1638–1649

    Article  PubMed  Google Scholar 

  • Yu FH, Catterall WA (2003) Overview of the voltage-gated sodium channel family. Genome Biol 4:207

    Article  PubMed  Google Scholar 

  • Zhang X, Davis JQ, Carpenter S, Bennett V (1998) Structural requirements for association of neurofascin with ankyrin. J Biol Chem 273:30785–30794

    Article  PubMed  CAS  Google Scholar 

  • Zhou D, Lambert S, Malen PL, Carpenter S, Boland LM, Bennett V (1998a) AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. J Cell Biol 143:1295–1304

    Article  CAS  Google Scholar 

  • Zhou L, Zhang CL, Messing A, Chiu SY (1998b) Temperature-sensitive neuromuscular transmission in Kv1.1 null mice: role of potassium channels under the myelin sheath in young nerves. J Neurosci 1:7200–7215

    Google Scholar 

  • Zhou L, Messing A, Chiu SY (1999) Determinants of excitability at transition zones in Kv1.1-deficient myelinated nerves. J Neurosci 19:5768–5781

    PubMed  CAS  Google Scholar 

  • Zonta B, Tait S, Melrose S, Anderson H, Harroch S, Higginson J, Sherman DL, Brophy PJ (2008) Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous system. J Cell Biol 181:1169–1177

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The work in our laboratory is supported by the grants from NIGMS and NINDS of the National Institutes of Health, National Multiple Sclerosis Society, and funds from the State of North Carolina.

Author information

Authors and Affiliations

  1. Department of Cell and Molecular Physiology, Curriculum in Neurobiology, UNC-Neuroscience Center and Neurodevelopmental Disorders Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, 27599-7545, USA

    Courtney Thaxton & Manzoor A. Bhat

Authors
  1. Courtney Thaxton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manzoor A. Bhat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manzoor A. Bhat .

Editor information

Editors and Affiliations

  1. Summer Hill Lane 70, Williamsville, 14221, U.S.A.

    Edward Koenig

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Thaxton, C., Bhat, M.A. (2009). Myelination and Regional Domain Differentiation of the Axon. In: Koenig, E. (eds) Cell Biology of the Axon. Results and Problems in Cell Differentiation, vol 48. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2009_3

Download citation

Publish with us

Policies and ethics

Search

Navigation