myelin p0 protein


Summary: A protein that accounts for more than half of the peripheral nervous system myelin protein. The extracellular domain of this protein is believed to engage in adhesive interactions and thus hold the myelin membrane compact. It can behave as a homophilic adhesion molecule through interactions with its extracellular domains. (From J Cell Biol 1994;126(4):1089-97)

Top Publications

  1. Brown A, Lemke G. Multiple regulatory elements control transcription of the peripheral myelin protein zero gene. J Biol Chem. 1997;272:28939-47 pubmed
    ..These core elements are essential for the transcription observed from the transfected promoter in cultured Schwann cells. ..
  2. Ey B, Kobsar I, Blazyca H, Kroner A, Martini R. Visualization of degenerating axons in a dysmyelinating mouse mutant with axonal loss. Mol Cell Neurosci. 2007;35:153-60 pubmed
  3. Nelis E, Haites N, Van Broeckhoven C. Mutations in the peripheral myelin genes and associated genes in inherited peripheral neuropathies. Hum Mutat. 1999;13:11-28 pubmed
    ..This large number of genetically defined patients provides an exceptional opportunity to examine the correlation between phenotype and genotype. ..
  4. Xu W, Shy M, Kamholz J, Elferink L, Xu G, Lilien J, et al. Mutations in the cytoplasmic domain of P0 reveal a role for PKC-mediated phosphorylation in adhesion and myelination. J Cell Biol. 2001;155:439-46 pubmed
    ..We conclude that PKC-mediated phosphorylation of specific residues within the cytoplasmic domain of P0 is necessary for P0-mediated adhesion, and alteration of this process can cause demyelinating neuropathy in humans. ..
  5. Yan W, Archelos J, Hartung H, Pollard J. P0 protein is a target antigen in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol. 2001;50:286-92 pubmed
  6. Carenini S, Maurer M, Werner A, Blazyca H, Toyka K, Schmid C, et al. The role of macrophages in demyelinating peripheral nervous system of mice heterozygously deficient in p0. J Cell Biol. 2001;152:301-8 pubmed
    ..These findings demonstrate an active role of macrophages during pathogenesis of inherited demyelination with putative impact on future treatment strategies. ..
  7. Rünker A, Kobsar I, Fink T, Loers G, Tilling T, Putthoff P, et al. Pathology of a mouse mutation in peripheral myelin protein P0 is characteristic of a severe and early onset form of human Charcot-Marie-Tooth type 1B disorder. J Cell Biol. 2004;165:565-73 pubmed
    ..Our observations support the view that the Ile106Leu mutation acts by a dominant-negative gain of function and that the P0sub-transgenic mouse represents an animal model for a severe, tomaculous form of CMT1B. ..
  8. Shapiro L, Doyle J, Hensley P, Colman D, Hendrickson W. Crystal structure of the extracellular domain from P0, the major structural protein of peripheral nerve myelin. Neuron. 1996;17:435-49 pubmed
    ..We report analytical ultracentrifugation data for P0ex that support this idea. ..
  9. Steck A, Erne B, Pareyson D, Sghirlanzoni A, Taroni F, Schaeren Wiemers N. Normal expression of myelin protein zero with frame-shift mutation correlates with mild phenotype. J Peripher Nerv Syst. 2006;11:61-6 pubmed
    ..In conclusion, we demonstrate that careful analysis of protein expression levels in peripheral nerve tissues provides important information with respect to the understanding of the molecular basis of these neuropathies. ..

More Information


  1. Jaegle M, Mandemakers W, Broos L, Zwart R, Karis A, Visser P, et al. The POU factor Oct-6 and Schwann cell differentiation. Science. 1996;273:507-10 pubmed
    ..Thus, Oct-6 appears to be required for the transition of promyelin cells to myelinating cells. Once these cells progress past this point, Oct-6 is no longer required, and myelination occurs normally. ..
  2. Piazza S, Baldinotti F, Fogli A, Conidi M, Michelucci A, Ienco E, et al. A new truncating MPZ mutation associated with a very mild CMT1 B phenotype. Neuromuscul Disord. 2010;20:817-9 pubmed publisher
    ..Our report expands the number of MPZ mutations and indicates that mutations in exon 4 may cause a mild Charcot-Marie-Tooth type 1B phenotype. ..
  3. Schneider Gold C, Kötting J, Epplen J, Gold R, Gerding W. Unusual Charcot-Marie-Tooth phenotype due to a mutation within the intracellular domain of myelin protein zero. Muscle Nerve. 2010;41:550-4 pubmed publisher
    ..The index patient responded to intravenous immunoglobulin and immunosuppression, so there may be a possible secondary autoimmune process, probably triggered by altered antigen presentation due to mutated MPZ protein. ..
  4. Martini R. P0-deficient knockout mice as tools to understand pathomechanisms in Charcot-Marie-Tooth 1B and P0-related Déjérine-Sottas syndrome. Ann N Y Acad Sci. 1999;883:273-80 pubmed
    ..These histological characteristics are instrumental in understanding the pathogenesis of the disease and may help in developing treatments. ..
  5. Choi B, Lee M, Shin S, Hwang J, Choi K, Kim W, et al. Mutational analysis of PMP22, MPZ, GJB1, EGR2 and NEFL in Korean Charcot-Marie-Tooth neuropathy patients. Hum Mutat. 2004;24:185-6 pubmed
    ..We described the identified mutations and phenotype-genotype correlations based on nerve conduction studies. ..
  6. Fasano A, Amoresano A, Rossano R, Carlone G, Carpentieri A, Liuzzi G, et al. The different forms of PNS myelin P0 protein within and outside lipid rafts. J Neurochem. 2008;107:291-301 pubmed publisher
    ..Our findings suggest that structural differences between the two proteins, mainly related to the glycogroups, might be responsible for their different localization. ..
  7. Carenini S, Montag D, Schachner M, Martini R. Subtle roles of neural cell adhesion molecule and myelin-associated glycoprotein during Schwann cell spiralling in P0-deficient mice. Glia. 1999;27:203-12 pubmed
    ..Because these functional roles are detectable only in the absence of P0, our results confirm the view that myelin-related molecules can play distinct, but also partially overlapping roles. ..
  8. D Urso D, Ehrhardt P, Muller H. Peripheral myelin protein 22 and protein zero: a novel association in peripheral nervous system myelin. J Neurosci. 1999;19:3396-403 pubmed
    ..Furthermore, these results propose a possible explanation why alterations in either of these molecules are sufficient to destabilize the myelin structure and cause a similar disease phenotype. ..
  9. Eichberg J. Myelin P0: new knowledge and new roles. Neurochem Res. 2002;27:1331-40 pubmed
    ..Besides its structural function in myelin, P0 may have roles in the delivery of other Schwann cell proteins to their proper location, especially at or near nodes of Ranvier, and in neuronal-glial interactions. ..
  10. Shy M. Peripheral neuropathies caused by mutations in the myelin protein zero. J Neurol Sci. 2006;242:55-66 pubmed
    ..Identifying molecular pathways involved in early and late onset CMT1B will be crucial to understand how MPZ mutations cause CMT1B so that rational therapies for both early and late onset neuropathies can be developed. ..
  11. Silander K, Meretoja P, Juvonen V, Ignatius J, Pihko H, Saarinen A, et al. Spectrum of mutations in Finnish patients with Charcot-Marie-Tooth disease and related neuropathies. Hum Mutat. 1998;12:59-68 pubmed
    ..Our mutation screening results show the necessity of molecular diagnosis, in addition to clinical and electrophysiological evaluation, for proper subtyping of the disease and for accurate genetic counseling. ..
  12. Avila R, Inouye H, Baek R, Yin X, Trapp B, Feltri M, et al. Structure and stability of internodal myelin in mouse models of hereditary neuropathy. J Neuropathol Exp Neurol. 2005;64:976-90 pubmed
    ..Our findings demonstrate that diffraction can provide a quantitative basis for understanding, at a molecular level, the membrane packing defects that occur in internodal myelin in demyelinating peripheral neuropathies...
  13. Shy M, Jani A, Krajewski K, Grandis M, Lewis R, Li J, et al. Phenotypic clustering in MPZ mutations. Brain. 2004;127:371-84 pubmed
    ..In contrast, late onset neuropathy is caused by mutations that more subtly alter myelin structure and which probably disrupt Schwann cell-axonal interactions. ..
  14. Thompson A, Cronin M, Kirschner D. Myelin protein zero exists as dimers and tetramers in native membranes of Xenopus laevis peripheral nerve. J Neurosci Res. 2002;67:766-71 pubmed
    ..Native gels showed dimeric P0 without the appearance of monomer or tetramer, suggesting that dimeric P0, the most prominent form of the protein, is the most stable and likely occurs in the native myelin membrane array. ..
  15. Martini R. Animal models for inherited peripheral neuropathies: chances to find treatment strategies?. J Neurosci Res. 2000;61:244-50 pubmed
    ..This review focusses on common pathways of pathogenesis of the disorders and emphasizes strategies that might be suitable to ameliorate disease expression. ..
  16. Plante Bordeneuve V, Guiochon Mantel A, Lacroix C, Lapresle J, Said G. The Roussy-Lévy family: from the original description to the gene. Ann Neurol. 1999;46:770-3 pubmed
    ..These findings show that the Roussy-Lévy family belongs to the CMT-1B subtype and has original morphological and genetic features. ..
  17. Wrabetz L, Feltri M, Quattrini A, Imperiale D, Previtali S, D Antonio M, et al. P(0) glycoprotein overexpression causes congenital hypomyelination of peripheral nerves. J Cell Biol. 2000;148:1021-34 pubmed
    ..These data reveal new points in nerve development at which Schwann cells are susceptible to increased gene dosage, and suggest a novel basis for hereditary neuropathy. ..
  18. Mersiyanova I, Ismailov S, Polyakov A, Dadali E, Fedotov V, Nelis E, et al. Screening for mutations in the peripheral myelin genes PMP22, MPZ and Cx32 (GJB1) in Russian Charcot-Marie-Tooth neuropathy patients. Hum Mutat. 2000;15:340-7 pubmed
    ..Phenotype-genotype correlations were based on nerve conduction velocity studies and mutation type. ..
  19. Trapp B. Distribution of the myelin-associated glycoprotein and P0 protein during myelin compaction in quaking mouse peripheral nerve. J Cell Biol. 1988;107:675-85 pubmed
    ..The failure of some quaking mouse Schwann cells to form compact myelin appears to result from an inability to remove the myelin-associated glycoprotein from their mesaxon membranes. ..
  20. Martini R, Mohajeri M, Kasper S, Giese K, Schachner M. Mice doubly deficient in the genes for P0 and myelin basic protein show that both proteins contribute to the formation of the major dense line in peripheral nerve myelin. J Neurosci. 1995;15:4488-95 pubmed
    ..Both molecules thus contribute to the formation of the major dense line and to the determination of myelin thickness. Furthermore, our observations modify the view that axon caliber is dependent on normal myelin. ..
  21. Feltri M, D Antonio M, Quattrini A, Numerato R, Arona M, Previtali S, et al. A novel P0 glycoprotein transgene activates expression of lacZ in myelin-forming Schwann cells. Eur J Neurosci. 1999;11:1577-86 pubmed
    ..These data suggest that intragenic or 3' flanking sequences are necessary to generate the remarkable levels of endogenous P0 gene expression. ..
  22. Martini R, Zielasek J, Toyka K, Giese K, Schachner M. Protein zero (P0)-deficient mice show myelin degeneration in peripheral nerves characteristic of inherited human neuropathies. Nat Genet. 1995;11:281-6 pubmed
    ..Thus, the pathology of homo- and heterozygous P0 mutants resembles that of the severely affected Déjérine-Sottas and the more mildly affected Charcot-Marie-Tooth type 1B patients, respectively. ..
  23. Ohnishi A, Yamamoto T, Yamamori S, Sudo K, Fukushima Y, Ikeda M. Myelinated fibers in Charcot-Marie-Tooth disease type 1B with Arg98His mutation of Po protein. J Neurol Sci. 1999;171:97-109 pubmed
    ..This study contributes to a better understanding of myelin abnormalities in patients with CMT type 1B and Arg98His or other similar extramembranous amino acid substitutions of Po protein. ..
  24. Wrabetz L, D Antonio M, Pennuto M, Dati G, Tinelli E, Fratta P, et al. Different intracellular pathomechanisms produce diverse Myelin Protein Zero neuropathies in transgenic mice. J Neurosci. 2006;26:2358-68 pubmed
    ..This is the first evidence for UPR in association with neuropathy and provides a model to determine whether and how mutant proteins can provoke demyelination from outside of myelin. ..
  25. Hayasaka K, Himoro M, Sawaishi Y, Nanao K, Takahashi T, Takada G, et al. De novo mutation of the myelin P0 gene in Dejerine-Sottas disease (hereditary motor and sensory neuropathy type III). Nat Genet. 1993;5:266-8 pubmed
    ..The results strongly suggest that a de novo dominant mutation of the P0 gene is responsible for at least some sporadic cases of Dejerine-Sottas disease. ..
  26. Burns T, Phillips L, Dimberg E, Vaught B, Klein C. Novel myelin protein zero mutation (Arg36Trp) in a patient with acute onset painful neuropathy. Neuromuscul Disord. 2006;16:308-10 pubmed
    ..We predict that other rapid symptom onset polyneuropathies will be found to have direct genetic susceptibility. ..
  27. Fabrizi G, Taioli F, Cavallaro T, Rigatelli F, Simonati A, Mariani G, et al. Focally folded myelin in Charcot-Marie-Tooth neuropathy type 1B with Ser49Leu in the myelin protein zero. Acta Neuropathol. 2000;100:299-304 pubmed
  28. Beaino W, Trifilieff E. Thiopalmitoylated peptides from the peripheral nervous system myelin p0 protein: synthesis, characterization, and neuritogenic properties. Bioconjug Chem. 2010;21:1439-47 pubmed publisher
  29. D Antonio M, Musner N, Scapin C, Ungaro D, Del Carro U, Ron D, et al. Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice. J Exp Med. 2013;210:821-38 pubmed publisher
    ..Resetting translational homeostasis may provide a therapeutic strategy in tissues impaired by misfolded proteins that are synthesized during terminal differentiation. ..
  30. Grandis M, Vigo T, Passalacqua M, Jain M, Scazzola S, La Padula V, et al. Different cellular and molecular mechanisms for early and late-onset myelin protein zero mutations. Hum Mol Genet. 2008;17:1877-89 pubmed publisher
    ..Further characterization of these pathways will lead to a better understanding of the pathogenesis of CMT1B and a rational basis for treating these debilitating inherited neuropathies. ..
  31. Pennuto M, Tinelli E, Malaguti M, Del Carro U, D Antonio M, Ron D, et al. Ablation of the UPR-mediator CHOP restores motor function and reduces demyelination in Charcot-Marie-Tooth 1B mice. Neuron. 2008;57:393-405 pubmed publisher
    ..S63del mice also provide an opportunity to explore how cells can dysfunction yet survive in prolonged ER stress-important for neurodegeneration related to misfolded proteins. ..
  32. Giese K, Martini R, Lemke G, Soriano P, Schachner M. Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Cell. 1992;71:565-76 pubmed
    ..They further suggest that this protein conveys a signal that regulates Schwann cell gene expression. ..
  33. Yin X, Kidd G, Wrabetz L, Feltri M, Messing A, Trapp B. Schwann cell myelination requires timely and precise targeting of P(0) protein. J Cell Biol. 2000;148:1009-20 pubmed
    ..These results indicate that P(0) gene multiplication causes P(0) mistargeting to mesaxon membranes, and through obligate P(0) homophilic adhesion, renders these dynamic membranes inert and halts myelination. ..
  34. Rautenstrauss B, Nelis E, Grehl H, Pfeiffer R, Van Broeckhoven C. Identification of a de novo insertional mutation in P0 in a patient with a Déjérine-Sottas syndrome (DSS) phenotype. Hum Mol Genet. 1994;3:1701-2 pubmed
  35. Hayasaka K, Himoro M, Sato W, Takada G, Uyemura K, Shimizu N, et al. Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene. Nat Genet. 1993;5:31-4 pubmed
    ..Individuals with CMT1B are heterozygous for the normal allele and the mutant allele. Our results indicate that P0 is a gene responsible for CMT1B. ..
  36. Hayasaka K, Takada G, Ionasescu V. Mutation of the myelin P0 gene in Charcot-Marie-Tooth neuropathy type 1B. Hum Mol Genet. 1993;2:1369-72 pubmed
    ..The results confirmed that P0 is a gene responsible for CMT1B. ..
  37. Filbin M, Zhang K, Li W, Gao Y. Characterization of the effect on adhesion of different mutations in myelin P0 protein. Ann N Y Acad Sci. 1999;883:160-7 pubmed
    ..This approach to address the functional consequences of mutations in P0 can now be used to assess the effects of different mutations associated with CMT1B. ..
  38. Schmid C, Stienekemeier M, Oehen S, Bootz F, Zielasek J, Gold R, et al. Immune deficiency in mouse models for inherited peripheral neuropathies leads to improved myelin maintenance. J Neurosci. 2000;20:729-35 pubmed
    ..We hypothesize that autoreactive immune cells can significantly foster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy. ..
  39. Menichella D, Xu W, Jiang H, Sohi J, Vallat J, Baron P, et al. The absence of myelin P0 protein produces a novel molecular phenotype in Schwann cells. Ann N Y Acad Sci. 1999;883:281-93 pubmed
  40. Kirschner D, Inouye H, Saavedra R. Membrane adhesion in peripheral myelin: good and bad wraps with protein P0. Structure. 1996;4:1239-44 pubmed
    ..These studies have proved useful in understanding the molecular basis of clinical phenotypes in certain demyelinating neuropathies. ..
  41. Thomas F, Lebo R, Rosoklija G, Ding X, Lovelace R, Latov N, et al. Tomaculous neuropathy in chromosome 1 Charcot-Marie-Tooth syndrome. Acta Neuropathol. 1994;87:91-7 pubmed
    ..The severity of the myelin abnormalities suggests that in this family Charcot-Marie-Tooth disease may result from a generalized disturbance of Schwann cells as a result of an abnormal P0 protein. ..
  42. Jang S, Svaren J. Induction of myelin protein zero by early growth response 2 through upstream and intragenic elements. J Biol Chem. 2009;284:20111-20 pubmed publisher
    ..Overall, these results provide a locus-wide analysis of the role and activity of Egr2 in regulation of the Mpz gene within its native chromosomal context. ..
  43. Trapp B, Quarles R. Presence of the myelin-associated glycoprotein correlates with alterations in the periodicity of peripheral myelin. J Cell Biol. 1982;92:877-82 pubmed
    ..The presence of MAG in these locations also suggests that MAG may serve a function in regulating myelination in the PNS. ..
  44. Lemke G, Axel R. Isolation and sequence of a cDNA encoding the major structural protein of peripheral myelin. Cell. 1985;40:501-8 pubmed
    ..Furthermore, we find that the induction of P0 mRNA coincides with the initiation of myelin formation, and we propose a model in which the glycoprotein serves as a molecular guidepost for this process. ..
  45. Miller L, Patzkó A, Lewis R, Shy M. Phenotypic presentation of the Ser63Del MPZ mutation. J Peripher Nerv Syst. 2012;17:197-200 pubmed publisher
    ..These results suggest that clinical presentation along cannot predict which MPZ mutations will be retained in the ER and activate the UPR. ..
  46. Lemke G, Lamar E, Patterson J. Isolation and analysis of the gene encoding peripheral myelin protein zero. Neuron. 1988;1:73-83 pubmed
  47. Leblanc S, Jang S, Ward R, Wrabetz L, Svaren J. Direct regulation of myelin protein zero expression by the Egr2 transactivator. J Biol Chem. 2006;281:5453-60 pubmed
  48. Guenard V, Schweitzer B, Flechsig E, Hemmi S, Martini R, Suter U, et al. Effective gene transfer of lacZ and P0 into Schwann cells of P0-deficient mice. Glia. 1999;25:165-78 pubmed
    ..Genetic repair of abnormal Schwann cells by using adenovirus vectors might be a possible technique to treat animal models of inherited peripheral neuropathies. ..
  49. Roa B, Warner L, Garcia C, Russo D, Lovelace R, Chance P, et al. Myelin protein zero (MPZ) gene mutations in nonduplication type 1 Charcot-Marie-Tooth disease. Hum Mutat. 1996;7:36-45 pubmed
    ..These observations provide further confirmation of the role of MPZ in CMT1B and suggest that MPZ coding region mutations may account for a limited percentage of disease-causing mutations in nonduplication CMT1 patients. ..
  50. Nicholson G. Mutation testing in Charcot-Marie-Tooth neuropathy. Ann N Y Acad Sci. 1999;883:383-8 pubmed
    ..It is concluded that "blind" testing of CMT1 families for connexin32, P0, and PMP22 mutations is of limited value. ..
  51. Xu W, Manichella D, Jiang H, Vallat J, Lilien J, Baron P, et al. Absence of P0 leads to the dysregulation of myelin gene expression and myelin morphogenesis. J Neurosci Res. 2000;60:714-24 pubmed
    ..Taken together, these results demonstrate that P0 is involved, either directly or indirectly, in the regulation of both myelin gene expression and myelin morphogenesis. ..
  52. Hilmi S, Fournier M, Valeins H, Gandar J, Bonnet J. Myelin P0 glycoprotein: identification of the site phosphorylated in vitro and in vivo by endogenous protein kinases. J Neurochem. 1995;64:902-7 pubmed
    ..Our results strongly suggest that the phosphorylation of these serine residues alters the secondary structure of this domain. Such a structural perturbation could play an important role in myelin compaction at the dense line level. ..
  53. Hayasaka K, Himoro M, Wang Y, Takata M, Minoshima S, Shimizu N, et al. Structure and chromosomal localization of the gene encoding the human myelin protein zero (MPZ). Genomics. 1993;17:755-8 pubmed
    ..The localization of the MPZ gene coincides with the locus for Charcot-Marie-Tooth disease type 1B, determined by linkage analysis. ..