Skip to main content
SpringerLink
Log in

Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease

  • Review Article
  • Published:
NeuroMolecular Medicine Aims and scope Submit manuscript

Abstract

We review the putative functions and malfunctions of proteins encoded by genes mutated in Charcot-Marie-Tooth disease (CMT; inherited motor and sensory neuropathies) in normal and affected peripheral nerves. Some proteins implicated in demyelinating CMT, peripheral myelin protein 22, protein zero (P0), and connexin32 (Cx32/GJB1) are crucial components of myelin. Periaxin is involved in connecting myelin to the surrounding basal lamina. Early growth response 2 (EGR2) and Sox10 are transcriptional regulators of myelin genes. Mutations in the small integral membrane protein of lysosome/late endosome, the myotubularin-related protein 2 (MTMR2), and MTMR13/set-binding factor 2 are involved in vesicle and membrane transport and the regulation of protein degradation. Pathomechanisms related to alterations of these processes are a widespread phenomenon in demyelinating neuropathies because mutations of myelin components may also affect protein biosynthesis, transport, and/or degradation. Related disease mechanisms are also involved inaxonal neuropathies although there is considerably more functional heterogeneity. Some mutations, most notably in P0, GJB1, ganglioside-induced differentiation-associated protein 1 (GDAP1), neurofilament light chain (NF-L), and dynamin 2 (DNM2), can result in demyelinating or axonal neuropathies introducing additional complexity in the pathogenesis. Often, this relates to the intinate connection between Schwann cells and neurons/axons leading to axonal damage even if the mutation-caused defect is Schwann-cell-autonomous. This mechanisms is likely for P0 and Cx32 mutations and provides the basis for the unifying hypothesis that also demyelinating neuropathies develop into functional axonopathies. In GDAP1 and DNM2 mutants, both Schwann cells and axons/neurons might be directly affected. NF-L mutants have a primary neuronal defect but also cause demyelination. The major challenge ahead lies in determining the individual contributions by neurons and Schwann cells to the pathology over time and to delineate the detailed molecular functions of the proteins associated with CMT in health and disease.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adlkofer K., Martini, R., Aguzzi A., Zielasek J., Toyka K. V., and Suter U. (1995) Hypermyelination and demyelinating peripheral neuropathy in Pmp22-deficient mice. Nat. Genet. 11, 274–280.

    PubMed  CAS  Google Scholar 

  • Adlkofer K., Naef R., and Suter U. (1997) Analysis of compound heterozygous mice reveals that the Trembler mutation can behave as a gain-of-function allele. J. Neurosci. Res. 49, 671–680.

    PubMed  CAS  Google Scholar 

  • Alexander C., Votruba M., Pesch U. E., et al. (2000) OPA1, enconding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat. Genet. 26, 211–215.

    PubMed  CAS  Google Scholar 

  • Arroyo E. J. and Scherer S. S. (2000) On the molecular architecture of myelinated fibers. Histochem. Cell Biol. 113, 1–18.

    PubMed  CAS  Google Scholar 

  • Azzedine H. Bolino A., Taieb T., et al. (2003) Mutations in MTMR13, a new pseud ophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma. Am. J. Hum. Genet. 72, M41-M53.

    Google Scholar 

  • Balice-Gordon R. J., Bone L. J., and Scherer S. S. (1998) Functional gap junctions in the schwann cell myelin sheath. J. Cell Biol. 142, 1095–1104.

    PubMed  CAS  Google Scholar 

  • Baxter R. V., Ben Othmane K., Rochelle J. M., et al. (2002) Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21. Nat. Genet. 30, 21,22.

    PubMed  CAS  Google Scholar 

  • Benndorf, R., Sun X., Gilmont R. R., e al. (2001) HSP22, a new member of the small heat shock protein superfamily, interacts with mimic of phosphorylated HSP27 ((3D)HSP27). J. Biol. Chem. 276, 26,753–26,761.

    CAS  Google Scholar 

  • Bennett C. L., Shirk A. J., Huynh H. M., et al. (2004) SIMPLE mutation in demyelinating neuropathy and distribution in sciatic nerve. Ann. Neurol. 55, 713–720.

    PubMed  CAS  Google Scholar 

  • Berger P., Berger I., Schaffitzel C., Tersar K., Volkmer B., and Suter U. (2006) Multi-level regulation of myotubularin-related protein-2 (mtmr2) phosphatase activity by myotubularin-related protein-13/set-binding factor-2 (MTMR13/SBF2) Hum. Mol. Genet. (Prepublication online).

  • Berger P., Bonneick S., Willi S., Wymann M., and Suter U. (2002) Loss of phosphatase activity in myotubularin-related protein 2 is associated with Charcot-Marie-Tooth disease type 4B1. Hum. Mol. Genet. 11, 1569–1579.

    PubMed  CAS  Google Scholar 

  • Berger P., Schaffitzel C., Berger I., Ban N., and Suter U. (2003) Membrane association of myotubularin-related protein 2 is mediated by a pleckstrin homology-GRAM domain and and coiled-coil dimerization module. Proc. Natl. Acad. Sci. USA 100, 12,177–12,182.

    CAS  Google Scholar 

  • Berger P., Sirkowski E. E., Scherer S. S., and Suter U. (2004) Expression analysis of the N-Myc downstream-regulated gene 1 indicates that myelinating Schwann cells are the primary disease target in hereditary motor and sensory neuropathy-Lom. Neurobiol. Dis. 17, 290–299.

    PubMed  CAS  Google Scholar 

  • Bolino A., Bolis A., Previtali S. C., et al (2004) Disruption of Mtmr2 produces CMT4B1-like neuropathy with myelin outfolding and impaired spermatogenesis. J. Cell Biol. 167, 711–721.

    PubMed  CAS  Google Scholar 

  • Bolino A., Muglia M., Conforti F. L., et al. (2000) Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat. Genet. 25, 17–19.

    PubMed  CAS  Google Scholar 

  • Bolis A., Coviello S., Bussini S., et al. (2005) Loss of Mtmr2 phosphatase in Schwann cells but not in motor neurons causes Charcot-Marie-Tooth type 4B1 neuropathy with myelin outfoldings. J. Neurosci. 25, 8567–8577.

    PubMed  CAS  Google Scholar 

  • Bomont P., Cavalier L., Blondeau F., et al. (2000) The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nat. Genet. 26, 370–374.

    PubMed  CAS  Google Scholar 

  • Bondurand N., Girard M., Pingault V., Lemort N., Dubourg O., and Goosens M. (2001) Human Connexin 32, a gap junction protein altered in the X-linked form of Charcot-Marie-Tooth disease, is directly regualted by the transcription factor SOX10. Hum. Mol. Genet. 10, 2783–2795.

    PubMed  CAS  Google Scholar 

  • Bonneick S., Boentert M., Berger P., et al. (2005) An animal model for Charcot-Marie-Tooth disease type 4B1 (CMT4B1). Hum. Mol. Genet. 14, 3685–3695.

    PubMed  CAS  Google Scholar 

  • Bossy-Wetzel E., Barosum M. J., Godzik A., Schwarzenbacher R., and Lipton S. A. (2003) Mitochondrial fission in apoptosis, neurodegeneration and aging. Curr. Opin. Cell Biol. 15, 706–716.

    PubMed  CAS  Google Scholar 

  • Brancolini C., Edomi P., Marzinotto S., and Schneider C. (2000) Exposure at the cells surface is required for gas3/PMP22 to regulate both cell death and cell spreading: implication for the Charcot-Marie-Tooth type 1A and Dejerine-Sottas diseases. Mol. Biol. Cell. 11, 2901–2914.

    PubMed  CAS  Google Scholar 

  • Brancolini C., Marzinotto S., Edomi P., et al. (1999) Rho-dependent regulation of cells spreading by the tetraspan membrane protein Gas3/PMP22. Mol. Biol. Cell 10, 2441–2459.

    PubMed  CAS  Google Scholar 

  • Britsch S., Goerich D. E., Riethmacher D., et al. (2001) The transcription factor Sox10 is a key regulator of peripheral glial development. Genes Dev. 15, 66–78.

    PubMed  CAS  Google Scholar 

  • Brownlees J., Ackerley S., Grierson A.J., et al. (2002) Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport. Hum. Mol. Genet. 11, 2837–2844.

    PubMed  CAS  Google Scholar 

  • Buccione R., Orth J. D., and McNiven M. A. (2004) Foot and mouth: podosomes, invadopodia and circular dorsal ruffles. Nat. Rev. Mol. Cell Biol. 5, 647–657.

    PubMed  CAS  Google Scholar 

  • Cailloux F., Gautheir-Barichard F., Mimault C., et al. (2000) Genotype-phenotype correlation, in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European network on brain dysmyelinating disease. Eur. J. Hum. Genet. 8, 837–845.

    PubMed  CAS  Google Scholar 

  • Carenini S., Neuberg D., Schachner M., Suter U., and Martini R. (1999) Localization and functional roles of PMP22 in peripheral nerves of P0-deficient mice. Glia 28, 256–264.

    PubMed  CAS  Google Scholar 

  • Chen H. and Chan D. C. (2004) Mitochondrial dynamics in mammals. Curr. Top. Dev. Biol. 59, 119–144.

    PubMed  CAS  Google Scholar 

  • Chen H., Chomyn A., and Chan D. C. (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J. Biol. Chem. 280, 26,185–26,192.

    CAS  Google Scholar 

  • Chen H., Detmer, S. A., Ewald A. J., Griffin E. E., Fraser S. E., and Chan D. C. (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J. Cell Biol. 160, 189–200.

    PubMed  CAS  Google Scholar 

  • Chies R., Nobbio, L., Edomi P., Schenone A., Schneider C., and Brancolini C. (2003) Alterations in the Arf6-regulated plasma membrane endoscomal recycling pathway in cells overexpressing the tetraspan protein Gas3/PMP22. J Cell Sci. 116, 987–999.

    PubMed  CAS  Google Scholar 

  • Ching G. Y. and Liem R. K. (1993) Assembly of type IV neuronal intermediate filaments in nonneuronal cells in the absence of preexisting cytoplasmic intermediate filaments. J. Cell Biol. 122, 1323–1335.

    PubMed  CAS  Google Scholar 

  • Choudhury A., Dominguez M., Puri V., et al. (2002) Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficiking in Niemann-Pick C cells. J. Clin. Invest. 109, 1541–1550.

    PubMed  CAS  Google Scholar 

  • Chubb J. R., Boyle, S., Perry P., and Bickmore W. A. (2002) Chromatin motion is constrained by association with nuclear compartments in human cells. Curr. Biol. 12, 439–445.

    PubMed  CAS  Google Scholar 

  • Cipolat S., Martins de Brito O., Dal Zilio B., and Scorrano L. (2004) OPA 1 requires mitofusin 1 to promote mitochondrial fusion. Proc. Natl. Acad. Sci. USA 101, 15,927–15,932.

    CAS  Google Scholar 

  • Colby J., Nicholson R., Dickson K. M., et al. (2000) PMP22 carrying the trembler or trembler-J mutation is intracellularly retained in myelinating Schwann cells. Neurobiol. Dis. 7, 561–573.

    PubMed  CAS  Google Scholar 

  • Court F. A., Sherman D. L., Pratt T., et al. (2004) Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves. Nature 431, 191–195.

    PubMed  CAS  Google Scholar 

  • Cuesta A., Pedrola L., Sevilla T., et al. (2002) The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease. Nat. Genet. 30, 22–25.

    PubMed  CAS  Google Scholar 

  • D'Urso D., Ehrhardt P., and Muller H. W. (1999) Peripheral myelin protein 22 and protein zero: a novel association in peripheral nervous system myelin. J. Neurosci. 19, 3396–3403.

    PubMed  Google Scholar 

  • D'Urso D., Prior, R., Greiner-Petter R., Gabreels-Festen A. A., and Muller H. W. (1998) Overloaded endoplasmic reticulum-Golgi compartments, a possible pathomechanism of peripheral neuropathies caused by mutations of the peripheral myelin protein PMP22. J. Neurosci. 18, 731–740.

    PubMed  Google Scholar 

  • Dang H., Li Z., Skolnik E. Y., and Fares H. (2004) Disease-related myotubularins function in endocytic traffic in Caenorhabditis elegans. Mol. Biol. Cell 15, 189–196.

    PubMed  CAS  Google Scholar 

  • Dawkins J. L., Hulme D. J., Brahmbhatt S. B., Auer-Grumbach M., and Nicholson G.A. (2001) Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat. Genet. 27, 309–312.

    PubMed  CAS  Google Scholar 

  • De Sandre-Giovannoli A., Chaouch M., Kozlov S. et al. (2002) Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse. Am. J. Hum. Genet. 70, 726–736.

    PubMed  Google Scholar 

  • Dickson K.M., Bergeron, J.J., Shames I., et al. (2002) Association of calnexin with mutant peripheral myelin protein-22 ex vivo: a basis for “gain-of-function” ER diseases. Proc. Natl. Acad. Sci. USA 99, 9852–9857.

    PubMed  CAS  Google Scholar 

  • Ding J., Liu J.J., Kowal A.S., et al. (2002) Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin. J. Cell Biol. 158, 427–433.

    PubMed  CAS  Google Scholar 

  • Dunn W. A., Jr. (1990) Studies on the mechanisms of autophagy: formation of the autophagic vacuole. J. Cell Biol. 110, 1923–1933.

    PubMed  Google Scholar 

  • Dytrych L., Sherman D. L., Gillespie C. S., and Brophy P. J. (1998) Two PDZ domain proteins encoded by the murine periaxin gene are the result of alternative intron retention and are differentially targeted in Schwann cells. J. Biol. Chem. 273, 5794–5800.

    PubMed  CAS  Google Scholar 

  • Edgar J. M. and Garbern J. (2004) The myelinated axon is dependent on the myelinating cell for support and maintenance: molecules involved. J. Neurosci. Res. 76, 593–598.

    PubMed  CAS  Google Scholar 

  • Evgrafov O. V., Mersiyanova I., Irobi J., et al. (2004) Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. Nat. Genet. 36, 602–606.

    PubMed  CAS  Google Scholar 

  • Fabbretti E., Edomi P., Brancolini, C., and Schneider C. (1995) Apoptotic phenotype induced by overexpression of wild-type gas3/PMP22: its relation to the demyelinating peripheral neuropathy CMT1A. Genes Dev. 9, 1846–1856.

    PubMed  CAS  Google Scholar 

  • Feltri M. L. and Wrabetz L. (2005) Laminins and their receptors in Schwann cells and hereditary neuropathies. J. Peripher. Nerv. Syst. 10, 128–143.

    PubMed  CAS  Google Scholar 

  • Filbin M. T., Zhang K., Li W., and Gao Y. (1999) Characterization of the effect on adhesion of different mutations in myelin P0 protein. Ann. N. Y. Acad. Sci. 883, 160–167.

    PubMed  CAS  Google Scholar 

  • Fortun J., Dunn W. A., Jr., Joy S., Li J., and Notterpek L. (2003) Emerging role for autophagy in the removal of aggresomes in Schwann cells. J. Neurosci. 23, 10,672–10,680.

    CAS  Google Scholar 

  • Fortun J., Li J., Go J., Fenstermaker A., Fletcher B. S., and Notterpek L. (2005) Impaired proteasome activity and accumulation of ubiquitinated substrates in a hereditary neuropathy model. J. Neurochem. 92, 1531–1541.

    PubMed  CAS  Google Scholar 

  • Garbern J. Y., Cambi F., Tang X. M., et al. (1997) Proteolipid protein is necessary in peripheral as well as central myelin. Neuron 19, 205–218.

    PubMed  CAS  Google Scholar 

  • Garcia M. L., Lobsiger C. S., Shah S. B., et al. (2003) NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth. J. Cell Biol. 163, 1011–1020.

    PubMed  CAS  Google Scholar 

  • Gaullier J. M., Simonsen A., D'Arrigo A., Bremnes B., Stenmark H., and Aasland R. (1998) FYVE fingers bind PtdIns(3)P. Nature 394, 432, 433.

    PubMed  CAS  Google Scholar 

  • Giambonini-Brugnoli G., Buchstaller J., Sommer L., Suter U., and Mantei N. (2005) Distinct disease mechanisms in peripheral neuropathies due to altered peripheral myelin protein 22 gene dosage or a Pmp22 point mutation. Neurobiol. Dis. 18, 656–668.

    PubMed  CAS  Google Scholar 

  • Giese K. P., Martini R., Lemke G., Soriano P., and Schachner M. (1992) Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Cell 71, 565–576.

    PubMed  CAS  Google Scholar 

  • Gillespie C. S., Sherman D. L., Fleetwood-Walker S. M., et al. (2000) Peripheral demyelination and neuropathic pain behavior in periaxin-deficient mice. Neuron 26, 523–531.

    PubMed  CAS  Google Scholar 

  • Gutierrez M. G., Munafo D. B., Beron W., and Colombo M. I. (2004) Rab7 is required for the normal progression of the autophagic pathway in mammalian cells. J. Cell Sci. 117, 2687–2697.

    PubMed  CAS  Google Scholar 

  • Hagedorn L., Suter U., and Sommer L. (1999) P0 and PMP22 mark a multipotent neural crest-derived cell type that displays community effects in response to TGF-beta family factors. Development 126, 3781–3794.

    PubMed  CAS  Google Scholar 

  • Hasse B., Bosse F., Hanenberg H., and Muller H. W. (2004) Peripheral myelin protein 22 kDa and protein zero: domain specific trans-interactions. Mol. Cell Neurosci. 27, 370–378.

    PubMed  CAS  Google Scholar 

  • Hirokawa N. and Takemura R. (2005) Molecular motors and mechanisms of directional transport in neurons. Nat. Rev. Neurosci. 6, 201–214.

    PubMed  CAS  Google Scholar 

  • Houlden H., Girard M., Cockerell C., et al. (2004) Connexin 32 promoter P2 mutations: a mechanism of peripheral nerve dysfunction. Ann. Neurol. 56, 730–734.

    PubMed  CAS  Google Scholar 

  • Howard J. and Hyman A. A. (2003) Dynamics and mechanics of the microtubule plus end. Nature 422, 753–758.

    PubMed  CAS  Google Scholar 

  • Hunter M., Angelicheva D., Tournev I., et al. (2005) NDRG1 interacts with APO A-I and A-II and is a functional candidate for the HDL-C QTL on 8q24. Biochem. Biophys. Res. Commun. 332, 982–992.

    PubMed  CAS  Google Scholar 

  • Hunter M., Bernard R., Freitas E., et al. (2003) Mutation screening of the N-myc downstream-regulated gene 1 (NDRG1) in patients with Charcot-Marie-Tooth Disease. Hum. Mutat. 22, 129–135.

    PubMed  CAS  Google Scholar 

  • Hutchison C. J. and Worman H. J. (2004) A-type lamins: guardians of the soma? Nat. Cell Biol. 6, 1062–1067.

    PubMed  CAS  Google Scholar 

  • Huxley C., Passage E., Manson A., et al. (1996) Construction of a mouse model of Charcot-Marie-Tooth disease type 1A by pronuclear injection of human YAC DNA. Hum. Mol. Genet. 5, 563–569.

    PubMed  CAS  Google Scholar 

  • Inoue K., Shilo K., Boerkoel C. F., et al. (2002) Congenital hypomyelinating neuropathy, central dysmyelination, and Waardenburg-Hirschsprung disease: phenotypes linked by SOX10 mutation. Ann. Neurol. 52, 836–842.

    PubMed  CAS  Google Scholar 

  • Irobi J., Van Impe K., Seeman P., et al. (2004) Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy. Nat. Genet. 36, 597–601.

    PubMed  CAS  Google Scholar 

  • Isaacs A. M., Jeans A., Oliver P. L., et al. (2002) Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy. Mol. Cell Neurosci. 21, 114–125.

    PubMed  CAS  Google Scholar 

  • Jessen K. R. and Mirsky R. (1999) Schwann cells and their precursors emerge as major regulators of nerve development. Trends Neurosci. 22, 402–410.

    PubMed  CAS  Google Scholar 

  • Jessen K. R. and Mirsky R. (2002) Signals that determine Schwann cell identity. J. Anat. 200, 367–376.

    PubMed  CAS  Google Scholar 

  • Jetten A. M. and Suter U. (2000) The peripheral myelin protein 22 and epithelial membrane protein family. Prog. Nucleic Acid Res. Mol. Biol. 64, 97–129.

    PubMed  CAS  Google Scholar 

  • Jolliffe C. N., Harvey K. F., Haines B. P., Parasivam, G., and Kumar S. (2000) Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4. Biochem. J. 351(3), 557–565.

    PubMed  CAS  Google Scholar 

  • Kaul R., Gao G. P., Balamurugan K., and Matalon R. (1993) Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease. Nat. Genet. 5, 118–123.

    PubMed  CAS  Google Scholar 

  • Kim J., Lo L., Dormand E., and Anderson D. J. (2003) SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells. Neuron 38, 17–31.

    PubMed  CAS  Google Scholar 

  • Koshiba T., Detmer S. A., Kaiser J. T., Chen H., McCaffery J. M., and Chan D. C. (2004) Structural basis of mitochondrial tethering by mitofusin complexes. Science 305, 858–862.

    PubMed  CAS  Google Scholar 

  • Kuhlenbaumer G., Young P., Oberwittler C., et al. (2002) Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene. Neurology 58, 1273–1276.

    PubMed  CAS  Google Scholar 

  • LaMonte B. H., Wallace K. E., Holloway B. A., et al. (2002) Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron 34, 715–727.

    PubMed  CAS  Google Scholar 

  • Laporte J., Hu L. J., Kretz C., et al. (1996) A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat. Genet. 13, 175–182.

    PubMed  CAS  Google Scholar 

  • Lariviere R. C. and Julien J. P. (2004) Functions of intermediate filaments in neuronal development and disease. J. Neurobiol. 58, 131–148.

    PubMed  CAS  Google Scholar 

  • Le N., Nagarajan R., Wang, J. Y., Araki T., Schmidt R. E., and Milbrandt J. (2005a) Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination. Proc. Natl. Acad. Sci. USA 102, 2596–2601.

    PubMed  CAS  Google Scholar 

  • Le N., Nagarajan R., Wang J. Y., et al. (2005b) Nab proteins are essential for peripheral nervous system myelination. Nat. Neurosci. 8, 932–940.

    PubMed  CAS  Google Scholar 

  • Leblanc S. E., Srinivasan R., Ferri C., et al. (2005) Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination. J. Neurochem. 93, 737–748.

    PubMed  CAS  Google Scholar 

  • Lee G. J., Roseman A. M., Saibil H. R., and Vierling E. (1997) A small heat shock protein stably binds heat-denatured model substrates and can maintain a substrate in a folding-competent state. EMBO J. 16, 659–671.

    PubMed  CAS  Google Scholar 

  • Lee M. K., Xu Z., Wong P. C., and Cleveland D. W. (1993) Neurofilaments are obligate heteropolymers in vivo. J. Cell Biol. 122, 1337–1350.

    PubMed  CAS  Google Scholar 

  • Liu N., Yamauchi J., and Shooter E. M. (2004) Recessive, but not dominant, mutations in peripheral myelin protein 22 gene show unique patterns of aggregation and intracellular trafficking. Neurobiol. Dis. 17, 300–309.

    PubMed  CAS  Google Scholar 

  • Ludes-Meyers J. H., Kil H., Bednarek A. K., Drake J., Bedford M. T., and Aldaz C. M. (2004) WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins. Oncogene 23, 5049–5055.

    PubMed  CAS  Google Scholar 

  • Lupski J. R. and Chance P. F. (2005) Hereditary motor and sensory neuropathies involving altered dosage or mutation of PMP22: the CMT1A duplication and HNPP deletion, In: Dyck P. J. and Thomas P. K. (eds). Peripheral Neuropathies, Philadelphia: Elsevier Saunders, Vol. 2. pp. 1659–1680.

    Google Scholar 

  • Magyar J. P., Martini R., Ruelicke T., et al. (1996) Impaired differentiation of Schwann cells in transgenic mice with increased PMP22 gene dosage. J. Neurosci. 16, 5351–5360.

    PubMed  CAS  Google Scholar 

  • Mahadevan A., Santosh V., Gayatri N., et al. (2000) Infantile neuroaxonal dystrophy and giant axonal neuropathy—overlap diseases of neuronal cytoskeletal elements in childhood? Clin. Neuropathol. 19, 221–229.

    PubMed  CAS  Google Scholar 

  • Martini R. (2001) The effect of myelinating Schwann cells on axons. Muscle Nerve 24, 456–466.

    PubMed  CAS  Google Scholar 

  • Martini R., Zielasek J., Toyka K. V., Giese K. P., and Schachner M. (1995) Protein zero (P0)-deficient miceshow myelin degeneration in peripheral nerves characteristic of inherited human neuropathies. Nat. Genet. 11, 281–286.

    PubMed  CAS  Google Scholar 

  • McNiven M. A. (2005) Dynamin in disease. Nat. Genet. 37, 215, 216.

    PubMed  CAS  Google Scholar 

  • McNiven M. A., Baldassarre M., and Buccione R. (2004) The role of dynamin in the assembly and function of podosomes and invadopodia. Front. Biosci. 9, 1944–1953.

    PubMed  CAS  Google Scholar 

  • Meggouh F., de Visser M., Arts W. F., De Coo R. I., van Schaik I. N., and Baas F. (2005) Early onset neuropathy in a compound form of Charcot-Marie-Tooth disease. Ann. Neurol. 57, 589–591.

    PubMed  Google Scholar 

  • Meier C., Dermietzel R., Davidson K. G., Yasumura T., and Rash J. E. (2004) Connexin32-containing gap junctions in Schwann cells at the internodal zone of partial myelin compaction and in Schmidt-Lanterman incisures. J. Neurosci. 24, 3186–3198.

    PubMed  CAS  Google Scholar 

  • Michailov G. V., Sereda M. W., Brinkmann B. G., et al. (2004) Axonal neuregulin-1 regulates myelin sheath thickness. Science 304, 700–703.

    PubMed  CAS  Google Scholar 

  • Mollaaghababa R. and Pavan W. J. (2003) The importance of having your SOX on: role of SOX10 in the development of neural crest-derived melanocytes and glia. Oncogene 22, 3024–3034.

    PubMed  CAS  Google Scholar 

  • Moriwaki Y., Begum N. A., Kobayashi M., Matsumoto M., Toyoshima K., and Seya T. (2001) Mycobacterium bovis Bacillus Calmette-Guerin and its cell wall complex induce a novel lysosomal membrane protein, SIMPLE, that bridges the missing link between lipopolysaccharide and p53-inducible gene, LITAF(PIG7), and estrogen-inducible gene, EET-1. J. Biol. Chem. 276, 23,065–23,076.

    CAS  Google Scholar 

  • Mounkes L. and Stewart C. L. (2004) Structural organization and functions of the nucleus in development, aging, and disease. Curr. Top. Dev. Biol. 61, 191–228.

    PubMed  CAS  Google Scholar 

  • Muller H. W. (2000) Tetraspan myelin protein PMP22 and demyelinating peripheral neuropathies: new facts and hypotheses. Glia 29, 182–185.

    PubMed  CAS  Google Scholar 

  • Naef R., Adlkofer K., Lescher B., and Suter U. (1997) Aberrant protein trafficking in Trembler suggests a disease mechanism for hereditary human peripheral neuropathies. Mol. Cell Neurosci. 9, 13–25.

    PubMed  CAS  Google Scholar 

  • Naef R. and Suter U. (1999) Impaired intracellular trafficking is a common disease mechanism of PMP22 point mutations in peripheral neuropathies. Neurobiol. Dis. 6, 1–14.

    PubMed  CAS  Google Scholar 

  • Nagarajan R., Svaren J., Le N., Araki T., Watson M., and Milbrandt J. (2001) EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression. Neuron 30, 355–368.

    PubMed  CAS  Google Scholar 

  • Nangaku M., Sato-Yoshitake R., Okada Y., et al. (1994) KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria. Cell 79, 1209–1220.

    PubMed  CAS  Google Scholar 

  • Nelis E., Erdem S., Van Den Bergh P. Y., et al. (2002) Mutations in GDAP1: autosomal recessive CMT with demyelination and axonopathy. Neurology 59, 1865–1872.

    PubMed  CAS  Google Scholar 

  • Neuberg D. H., Sancho S., and Suter U. (1999) Altered molecular architecture of peripheral nerves in mice lacking the peripheral myelin protein 22 or connexin32. J. Neurosci. Res. 58, 612–623.

    PubMed  CAS  Google Scholar 

  • Neuspiel M., Zunino R., Gangaraju S., Rippstein P., and McBride H. (2005) Activated mitofusin 2 signals mitochondrial fusion, interferes with bax activation, and reduces susceptibility to radical induced depolarization. J. Biol. Chem. 280, 25,060–25,070.

    CAS  Google Scholar 

  • Niemann A., Rueegg M., La Padula V., Schenone A., and Suter U. (2005) Ganglioside-induced differentiation associated protein 1 (GDAP1) is a regulator of the mitochondrial network—new implications for Charcot-Marie-Tooth disease. J. Cell Biol. 170, 1067–1078.

    PubMed  CAS  Google Scholar 

  • Niemann S., Sereda M. W., Suter U., Griffiths I. R., and Nave K. A. (2000) Uncoupling of myelin assembly and schwann cell differentiation by transgenic overexpression of peripheral myelin protein 22. J. Neurosci. 20, 4120–4128.

    PubMed  CAS  Google Scholar 

  • Notterpek L., Roux K. J., Amici S. A., Yazdanpour A., Rahner C., and Fletcher B. S. (2001) Peripheral myelin protein 22 is a constituent of intercellular junctions in epithelia. Proc. Natl. Acad. Sci. USA 98, 14,404–14,409.

    CAS  Google Scholar 

  • Notterpek L., Ryan M. C., Tobler A. R., and Shooter E. M. (1999) PMP22 accumulation in aggresomes: implications for CMT1A pathology. Neurobiol. Dis. 6, 450–460.

    PubMed  CAS  Google Scholar 

  • Notterpek L., Shooter E. M., and Snipes G. J. (1997) Upregulation of the endosomal-lysosomal pathway in the trembler-J neuropathy. J. Neurosci. 17, 4190–4200.

    PubMed  CAS  Google Scholar 

  • Okuda T., Higashi Y., Kokame K., Tanaka C., Kondoh H., and Miyata T. (2004) N drg1-deficient mice exhibit a progressive demyelinating disorder of peripheral nerves. Mol. Cell Biol. 24, 3949–3956.

    PubMed  CAS  Google Scholar 

  • Olichon A., Baricault L., Gas N., et al. (2003) Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome crelease and apoptosis. J. Biol. Chem. 278, 7743–7746.

    PubMed  CAS  Google Scholar 

  • Orth J. D. and McNiven M. A. (2003) Dynamin at the actin-membrane interface. Curr. Opin. Cell Biol. 15, 31–39.

    PubMed  CAS  Google Scholar 

  • Paratore C., Goerich D. E., Suter U., Wegner M., and Sommer L. (2001) Survival and glial fate acquisition of neural crest cells are regulated by an interplay between the transcription factors Sox10 and extrinsic combinatorial signaling. Development 128, 3949–3961.

    PubMed  CAS  Google Scholar 

  • Pareek S., Notterpek L., Snipes G. J., et al. (1997) Neurons promote the translocation of peripheral myelin protein 22 into myelin. J. Neurosci. 17, 7754–7762.

    PubMed  CAS  Google Scholar 

  • Pareek S., Suter U., Snipes G. J., Welcher A. A., Shooter E. M., and Murphy R. A. (1993) Detection and processing of peripheral myelin protein PMP22 in cultured Schwann cells. J. Biol. Chem. 268, 10,372–10,379.

    CAS  Google Scholar 

  • Parkinson D. B., Bhaskaran A., Droggiti A., et al. (2004) Krox-20 inhibits Jun-NH2-terminal kinase/c-Jun to control Schwann cell proliferation and death. J. Cell Biol. 164, 385–394.

    PubMed  CAS  Google Scholar 

  • Passage E., Norreel J. C., Noack-Fraissignes P., et al. (2004) Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease. Nat. Med. 10, 396–401.

    PubMed  CAS  Google Scholar 

  • Pedrola L., Espert A., Wu X., Claramunt R., Shy M. E., and Palau F. (2005) GDAP1, the protein causing Charcot-Marie-Tooth disease type4A, is expressed in neurons and is associated with mitochondria. Hum. Mol. Genet. 14, 1087–1094.

    PubMed  CAS  Google Scholar 

  • Peirano R. I., Goerich D. E., Riethmacher D., and Wegner M. (2000) Protein zero gene expression is regulated by the glial transcription factor Sox10. Mol. Cell Biol. 20, 3198–3209.

    PubMed  CAS  Google Scholar 

  • Peirano R. I. and Wegner M. (2000) The glial transcription factor Sox10 binds to DNA both as monomer and dimer with different functional consequences. Nucleic Acids Res. 28, 3047–3055.

    PubMed  CAS  Google Scholar 

  • Perez-Olle R., Jones S. T., and Liem R. K. (2004) Phenotypic analysis of neurofilament light gene mutations linked to Charcot-Marie-Tooth disease in cell culture models. Hum. Mol. Genet. 13, 2207–2220.

    PubMed  CAS  Google Scholar 

  • Perez-Olle R., Leung C. L., and Liem R. K. (2002) Effects of Charcot-Marie-Tooth-linked mutations of the neurofilament light subunit on intermediate filament formation. J. Cell Sci. 115, 4937–4946.

    PubMed  CAS  Google Scholar 

  • Perez-Olle R., Lopez-Toledano M. A., Goryunov D., et al. (2005) Mutations in the neurofilament light gene linked to Charcot-Marie-Tooth disease cause defects in transport. J Neurochem. 93, 861–874.

    PubMed  CAS  Google Scholar 

  • Perfettini J. L., Roumier T., and Koremer G. (2005) Mitochondrial fusion and fission in the control of apoptosis. Trends Cell Biol. 15, 179–183.

    PubMed  CAS  Google Scholar 

  • Pich S., Bach D., Briones P., et al. (2005) The Characot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum. Mol. Genet. 14, 1405–1415.

    PubMed  CAS  Google Scholar 

  • Pintard L., Willems A., and Peter M. (2004) Cullin-based ubiquitin ligases: Cul3-BTB complexes join the family. EMBO J. 23, 1681–1687.

    PubMed  CAS  Google Scholar 

  • Poliak S. and Peles E. (2003) The local differentiation of myelinated axons at nodes of Ranvier. Nat. Rev. Neurosci. 4, 968–980.

    PubMed  CAS  Google Scholar 

  • Pornillos O., Alam S. L., Davis D. R., and Sundquist W. I. (2002) Structure of the Tsg 101 UEV domain in complex with the PTAP motif of the HIV-1 p6 protein. Nat. Struct. Biol. 9, 812–817.

    PubMed  CAS  Google Scholar 

  • Praefcke G. J. and McMahon H. T. (2004) The dynamin superfamily: universal membrane tubulation and fission molecules? Nat. Rev. Mol. Cell Biol. 5, 133–147.

    PubMed  CAS  Google Scholar 

  • Previtali S. C., Quattrini A., Fasolini M., et al. (2000) Epitope-tagged P(0) glycoprotein causes Charcot-Marie-Tooth-like neuropathy in transgenic mice. J. Cell Biol. 151, 1035–1046.

    PubMed  CAS  Google Scholar 

  • Previtali S. C., Zerega B., Sherman D. L., et al. (2003) Myotubularin-related 2 protein phosphatase and neurofilament light chain protein, both mutated in CMT neuropathies, interact in peripheral nerve. Hum. Mol. Genet. 12, 1713–1723.

    PubMed  CAS  Google Scholar 

  • Puls I., Jonnakuty C., LaMonte B. H., et al. (2003) Mutant dynactin in motor neuron disease. Nat. Genet. 33, 455–456.

    PubMed  CAS  Google Scholar 

  • Rappoport J. Z. and Simon S. M. (2003) Real-time analysis of clathrin-mediated endocytosis during cell migration. J. Cell Sci. 116, 847–855.

    PubMed  CAS  Google Scholar 

  • Bobinson F. L. and Dixon J. E. (2005) The phosphoinositide 3-phosphatase MTMR2 associated with MTMR13, a novel membrane-associated pseudophosphatase also mutated in type 4B Charcot-Marie-tooth disease. J. Biol. Chem. 280, 31,699–31,707.

    Google Scholar 

  • Rojo M., Legros F., Chateau D., and Lombes A. (2002) Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J. Cell Sci. 115, 1663–1674.

    PubMed  CAS  Google Scholar 

  • Roux K. J., Amici S. A., Fletcher B. S., and Notterpek L. (2005) Modulation of epithelial morphology, monolayer permeability, and cell migration by growth arrest specific 3/peripheral myelin protein 22. Mol. Biol. Cell 16, 1142–1151.

    PubMed  CAS  Google Scholar 

  • Roux K. J., Amici S. A., and Notterpek L. (2004) The temporospatial expression of peripheral myelin protein 22 at the developing blood-nerve and blood-brain barriers. J. Comp. Neurol. 474, 578–588.

    PubMed  CAS  Google Scholar 

  • Roy S. and Rauk A. (2005) Alzheimer's disease and the ‘ABSENT’ hypothesis: mechanism for amyloid beta endothelial and neuronal toxicity. Med. Hypotheses 65, 123–137.

    PubMed  CAS  Google Scholar 

  • Ryan M. C., Shooter E. M., and Notterpek L. (2002) Aggresome formation in neuropathy models based on peripheral myelin protein 22 mutations. Neurobiol. Dis. 10, 109–118.

    PubMed  CAS  Google Scholar 

  • Saifi G. M., Szigeti K., Snipes G. J., Garcia C. A., and Lupski J. R. (2003) Molecular mechanisms diagnosis, and rational approaches to management of and therapy for Charcot-Marie-Tooth disease and related peripheral neuropathies. J. Investig. Med. 51, 261–283.

    PubMed  CAS  Google Scholar 

  • Saifi G. M., Szigeti K., Wiszniewski W., et al. (2005) SIMPLE mutations in Charcot-Marie-Tooth disease and the potential role of its protein product in protein degradation. Hum. Mutat. 25, 372–383.

    PubMed  CAS  Google Scholar 

  • Saito M., Hayashi Y., Suzuki T., Tanaka H., Hozumi I., and Tsuji S. (1997) Linkage mapping of the gene for Charcot-Marie-Tooth disease type 2 to chromosome 1p(CMT2A) and the clinical features of CMT2A. Neurology 49, 1630–1635.

    PubMed  CAS  Google Scholar 

  • Salzer J. L. (2003) Polarized domains of myelinated axons. Neuron 40, 297–318.

    PubMed  CAS  Google Scholar 

  • Sancho S., Young P., and Suter U. (2001) Regulation of Schwann cell proliferation and apoptosis in PMP22-deficient mice and mouse models of Charcot-Marie-Tooth disease type 1A. Brain 124, 2177–2187.

    PubMed  CAS  Google Scholar 

  • Santel A. and Fuller M. T. (2001) Control of mitochondrial morphology by a human mitofusin. J. Cell Sci. 114, 867–874.

    PubMed  CAS  Google Scholar 

  • Scherer S. S. and Arroyo E. J. (2002) Recent progress on the molecular organization of myelinated axons. J. Peripher. Nerv. Syst 7, 1–12.

    PubMed  CAS  Google Scholar 

  • Scherer S. and Paul D. L. (2004) The Connexin 32 and Connexin29 Genes, In: Lazzarini R. A. (ed). Myelin Biology and Disorders. Elsevier Academic, San Diego, pp. 599–608.

    Google Scholar 

  • Scherer S. S., Xu Y. T., Messing A., Willecke K., Fischbeck K. H., and Jeng L. J. (2005) Transgenic expression of human connexin32 in myelinating Schwann cells prevents demyelination in connexin32-null mice. J. Neurosci. 25, 1550–1559.

    PubMed  CAS  Google Scholar 

  • Senderek J., Bergmann C., Stendel C., et al. (2003a) Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy. Am J. Hum. Genet. 73, 1106–1119.

    PubMed  CAS  Google Scholar 

  • Senderek J., Bergmann C., Weber S., et al. (2003b) Mutation of the SBF2 gene, encoding a novel member of the myotubularin family, in Charcot-Marie-Tooth neuropathy type 4B2/11p15. Hum. Mol. Genet. 12, 349–356.

    PubMed  CAS  Google Scholar 

  • Sereda M., Griffiths I., Puhlhofer A., et al. (1996) A rat transgenic model for Charcot-Marie-Tooth disease. Neuron 16, 1049–1060.

    PubMed  CAS  Google Scholar 

  • Sereda M. W., Meyer zu Horste G., Suter U., Uzma N., and Nave K. A. (2003) Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A). Nat. Med. 9, 1533–1537.

    PubMed  CAS  Google Scholar 

  • Shames I., Fraser A., Colby J., Orfali W., and Snipes G. J. (2003) Phenotypic differences between peripheral myelin protein-22 (PMP22) and myelin protein zero (P0) mutations associated with Charcot-Marie-Tooth-related diseases. J. Neuropathol. Exp. Neurol. 62, 751–764.

    PubMed  CAS  Google Scholar 

  • Shapiro L., Doyle J. P., Hensley P., Colman D. R., and Hendrickson W. A. (1996). Crystal structure of the extracellular domain from P0, the major structural protein of peripheral nerve myelin. Neuron 17, 435–449.

    PubMed  CAS  Google Scholar 

  • Sherman D. L., Fabrizi C., Gillespie C. S., and Brophy P. J. (2001) Specific disruption of a schwann cell dystrophin-related protein complex in a demyelinating neuropathy. Neuron 30, 677–687.

    PubMed  CAS  Google Scholar 

  • Shisheva A., Rusin B., Ikonomov O. C., DeMarco C., and Sbrissa D. (2001) Localization and insulin-regulated relocation of phosphoinositide 5-kinase PIKfyve in 3T3-L1 adipocytes. J. Biol. Chem. 276, 11,859–11,869.

    CAS  Google Scholar 

  • Shy M. E. (2004). Charcot-Marie-Tooth disease: an update. Curr. Opin. Neurol. 17, 579–585.

    PubMed  CAS  Google Scholar 

  • Shy M. E., Hobson G., Jain M., et al. (2003) Schwann cell expression of PLP1 but not DM20 is necessary to prevent neuropathy. Ann. Neurol. 53, 354–365.

    PubMed  CAS  Google Scholar 

  • Sivakumar K., Kyriakides T., Puls I., et al. (2005) Phenotypic spectrum of disorders associated with glycyl-tRNA synthetase mutations. Brain. 128, 2304–2314.

    PubMed  Google Scholar 

  • Snipes G. J., Suter J., Welcher A. A., and Shooter E. M. (1992) Characterization of a novel peripheral nervous system myelin protein (PMP-22/SR13). J. cell Biol. 117, 225–238.

    PubMed  CAS  Google Scholar 

  • Southwood C. M., Garbern J., Jiang W., and Gow A. (2002) The unfolded protein response modulates disease severity in Pelizaeus-Merzbacher disease. Neuron 36, 585–596.

    PubMed  CAS  Google Scholar 

  • Stogios P. J. and Prive G. G. (2004) The BACK domain in BTB-kelch proteins. Trends Biochem. Sci. 29, 634–637.

    PubMed  CAS  Google Scholar 

  • Straub B. K., Boda J., Kuhn C., et al. (2003) A novel cell-cell junction system: the cortex adhaerens mosaic of lens fiber cells. J. Cell Sci. 116, 4985–4995.

    PubMed  CAS  Google Scholar 

  • Sugiki T., Taketomi Y., Kikuchi-Yanoshita R., Murakami M., and Kudo I. (2004) Association of N-myc down-regulated gene 1 with heat-shock cognate protein 70 in mast cells. Biol. Pharm. Bull. 27, 628–633.

    PubMed  CAS  Google Scholar 

  • Sun X., Fontaine J. M., Rest J. S., Shelden E. A., Welsh M. J., and Benndorf R. (2004) Interaction of human HSP22 (HSPB8) with other small heat shock proteins. J. Biol. Chem. 279, 2394–2402.

    PubMed  CAS  Google Scholar 

  • Sun Y. and MacRae T. H. (2005) The small heat shock proteins and their role in human disease. FEBS J. 272, 2613–2627.

    PubMed  CAS  Google Scholar 

  • Suter U. (2004) PMP22 gene, In: Lazzarini R. A. (ed.) Myelin Biology and Disorders. Elsevier Academic, San Diego, pp. 547–564.

    Google Scholar 

  • Suter U., Moskow J. J., Welcher A. A., et al. (1992a). A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse. Proc. Natl. Acad. Sci. USA 89, 4382–4386.

    PubMed  CAS  Google Scholar 

  • Suter U. and Scherer S. S. (2003) Disease mechanisms in inherited neuropathies. Nat. Rev. Neurosci. 4, 714–726.

    PubMed  CAS  Google Scholar 

  • Suter U. and Snipes G. J. (1995) Biology and genetics of hereditary motor and sensory neuropathies. Annu. Rev. Neurosci. 18, 45–75.

    PubMed  CAS  Google Scholar 

  • Suter U., Welcher A. A., Ozcelik T., et al. (1992b) Trembler mouse carries a point mutation in a myelin gene. Nature 356, 241–244.

    PubMed  CAS  Google Scholar 

  • Takashima H., Boerkoel C. F., De Jonghe P., et al. (2002) Periaxin mutations cause a broad spectrum of demyelinating neuropathies. Ann. Neurol. 51, 709–715.

    PubMed  CAS  Google Scholar 

  • Taylor V., Zgraggen C., Naef R., and Suter U. (2000) Membrane topology of peripheral myelin protein 22. J. Neurosci. Res. 62, 15–27.

    PubMed  CAS  Google Scholar 

  • Tazir M., Azzedine H., Assami S., et al. (2004) Phenotypic variability in autosomal recessive axonal Charcot-Marie-Tooth disease due to the R298C mutation in lamin A/C. Brain 127, 154–163.

    PubMed  CAS  Google Scholar 

  • Thompson H. M., Cao H., Chen J., Euteneuer U., and McNiven M. A. (2004) Dynamin 2 binds gamma-tubulin and participates in centrosome cohesion. Nat. Cell Biol. 6, 335–342.

    PubMed  CAS  Google Scholar 

  • Tobler A. R., Liu N., Mueller L., and Shooter E. M. (2002) Differential aggregation of the Trembler and Trembler J mutants of peripheral myelin protein 22. Proc. Natl. Acad. Sci. USA 99, 483–488.

    PubMed  CAS  Google Scholar 

  • Tobler A. R., Notterpek L., Naef R., Taylor V., Suter U., and Shooter E. M. (1999) Transport of trembler-J mutant peripheral myelin protein 22 is blocked in the intermediate compartment and affects the transport of the wild-type protein by direct interaction. J. Neurosci. 19, 2027–2036.

    PubMed  CAS  Google Scholar 

  • Topiko P., Schneider-Maunoury S., Levi G., et al. (1994) Krox-20 controls myelination in the peripheral nervous system. Nature 371, 796–799.

    Google Scholar 

  • Vaurs-Barriere C., Wong K., Weibel T. D., et al. (2003) Insertion of mutant proteolipid protein results in missorting of myelin proteins. Ann. Neurol. 54, 769–780.

    PubMed  CAS  Google Scholar 

  • Verhoeven K., De Jonghe P., Coen K., et al. (2003) Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy. Am. J. Hum. Genet. 72, 722–727.

    PubMed  CAS  Google Scholar 

  • Vonderheit A. and Helenius A. (2005) Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes. PLoS Biol. 3, e233.

    PubMed  Google Scholar 

  • Wagner O. I., Ascano J., Tokito M., Leterrier J. F., Janmey P. A., and Holzbaur E. L. (2004) The interaction of neurofilaments with the microtubule motor cytoplasmic dynein. Mol. Biol. Cell 15, 5092–5100.

    PubMed  CAS  Google Scholar 

  • Walker D. M., Urbe S., Dove S. K., Tenza D., Raposo G., and Clague M. J. (2001) Characterization of MTMR3. an inositol lipid 3-phosphatase with novel substrate specificity. Curr. Biol. 11, 1600–1605.

    PubMed  CAS  Google Scholar 

  • Warner L. E., Mancias P., Butler I. J., et al. (1998) Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Nat. Genet. 18, 382–384.

    PubMed  CAS  Google Scholar 

  • Warner L. E., Svaren J., Milbrandt J., and Lupski J. R. (1999) Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies. Hum. Mol. Genet. 8, 1245–1251.

    PubMed  CAS  Google Scholar 

  • Wishart M. J. and Dixon J. E. (2002) PTEN and myotubularin phosphatases: from 3-phosphoinositide dephosphorylation to disease. Phosphatase and tensin homolog deleted on chromosometen. Trends Cell Biol. 12, 579–585.

    PubMed  CAS  Google Scholar 

  • Woese C. R., Olsen G. J., Ibba M., and Soll D. (2000) Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process. Microbiol. Mol. Biol. Rev. 64, 202–236.

    PubMed  CAS  Google Scholar 

  • Xia C. H., Roberts E. A., Her L. S., et al. (2003) Abnormal neurofilament transport caused by targeted disruption of neuronal kines in heavy chain KIF5A. J. Cell Biol. 161, 55–66.

    PubMed  CAS  Google Scholar 

  • Xu Z., Marszalek J. R., Lee M. K., et al. (1996) Subunit composition of neurofilaments specifies axonal diameter. J. Cell Biol. 133, 1061–1069.

    PubMed  CAS  Google Scholar 

  • Yin X., Kidd G. J., Wrabetz L., Feltri M. L., Messing A., and Trapp B. D. (2000) Schwann cell myelination requires timely and precise targeting of P(0) protein. J. Cell Biol. 148, 1009–1020.

    PubMed  CAS  Google Scholar 

  • Zhao C., Takita J., Tanaka Y., et al. (2001) Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell 105, 587–597.

    PubMed  CAS  Google Scholar 

  • Züchner S., Mersiyanova I. V., Muglia M., et al., (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat. Genet. 36, 449–451.

    PubMed  Google Scholar 

  • Züchner S., Noureddine M., Kennerson M., et al. (2005) Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease. Nat. Genet. 37, 289–294.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093, Zürich, Switzerland

    Axel Niemann, Philipp Berger & Ueli Suter

Authors
  1. Axel Niemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philipp Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ueli Suter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ueli Suter.

Additional information

The authors Niemann and Berger contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Niemann, A., Berger, P. & Suter, U. Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease. Neuromol Med 8, 217–241 (2006). https://doi.org/10.1385/NMM:8:1-2:217

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1385/NMM:8:1-2:217

Index Entries

Search

Navigation