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The Role of the Gap Junction Protein Connexin32 in the Myelin Sheath

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Cell Biology and Pathology of Myelin

Part of the book series: Altschul Symposia Series ((ALSS,volume 4))

Summary

X-linked Charcot-Marie-Tooth disease (CMTX) is caused by mutations in the gap junction gene connexin32 (Cx32). To date, 89 different mutations have been found, including deletions, insertions, missense, and nonsense mutations, and at least two mutations in the non-coding region. Different mutations appear to have different effects on the synthesis and localization of Cx32 protein. Both myelinating Schwann cells and oligodendrocytes express Cx32 mRNA and protein, and the localization of Cx32 protein matches the location of putative gap junctions previously seen by freeze-fracture electron microscopy. In myelinating Schwann cells, Cx32 protein is found in incisures and paranodes. Preliminary data suggest that gap junctions form a radial channel that directly traverses the myelin sheath. It is plausible that mutations in Cx32 disrupt the gap junctions in the myelin sheath, thereby abolishing this radial pathway and leading to peripheral neuropathy.

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Authors and Affiliations

  1. Department of Neurology, The University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104, USA

    Steven S. Scherer M.D., Ph.D. & Kenneth Fischbeck

  2. Department of Molecular and Cellular Biology, The University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104, USA

    Linda J. Bone & Suzanne M. Deschênes

  3. Department of Neuroscience, The University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104, USA

    Rita J. Balice-Gordon

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  1. University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    Bernhard H. J. Juurlink , Richard M. Devon , J. Ronald Doucette , Adil J. Nazarali , David J. Schreyer  & Valerie M. K. Verge , , , ,  & 

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Scherer, S.S., Bone, L.J., Deschênes, S.M., Fischbeck, K., Balice-Gordon, R.J. (1997). The Role of the Gap Junction Protein Connexin32 in the Myelin Sheath. In: Juurlink, B.H.J., Devon, R.M., Doucette, J.R., Nazarali, A.J., Schreyer, D.J., Verge, V.M.K. (eds) Cell Biology and Pathology of Myelin. Altschul Symposia Series, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5949-8_9

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