Changes in permeability caused by connexin 32 mutations underlie X- linked Charcot-Marie-Tooth disease

Seunghoon Oh, Yi Ri, Michael V. L. Bennett, E. Brady Trexler, Vytautas Verselis, Thaddeus A. Bargiello

Research output: Contribution to journalArticle

211 Citations (Scopus)

Abstract

The relationship between the loss of connexin 32 function and clinical manifestations of X-linked Charcot-Marie-Tooth (CMTX) disease is unknown. Here, we report that eight of nine CMTX mutations investigated form channels with measurable electrical conductance. Single-channel studies of two mutations demonstrate reduced junctional permeability caused by a decrease in either pore size (S26L) or open channel probability (M34T) that favors residency in a low-conductance substate. Permeation of second messengers such as cAMP through reflexive gap junctions between adjacent cytoplasmic loops of myelinating Schwann cells is likely to be reduced or absent in these channels. We propose that CMTX mutations impair the transduction of signals arising from normal glial-neuronal interactions and thereby cause demyelination and axonal degeneration.

Original languageEnglish (US)
Pages (from-to)927-938
Number of pages12
JournalNeuron
Volume19
Issue number4
DOIs
StatePublished - Oct 1997

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Charcot-Marie-Tooth Disease
Permeability
Mutation
Gap Junctions
Schwann Cells
Second Messenger Systems
Demyelinating Diseases
Internship and Residency
Neuroglia
Signal Transduction
connexin 32

ASJC Scopus subject areas

  • Neuroscience(all)

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Changes in permeability caused by connexin 32 mutations underlie X- linked Charcot-Marie-Tooth disease. / Oh, Seunghoon; Ri, Yi; Bennett, Michael V. L.; Trexler, E. Brady; Verselis, Vytautas; Bargiello, Thaddeus A.

In: Neuron, Vol. 19, No. 4, 10.1997, p. 927-938.

Research output: Contribution to journalArticle

Oh, Seunghoon ; Ri, Yi ; Bennett, Michael V. L. ; Trexler, E. Brady ; Verselis, Vytautas ; Bargiello, Thaddeus A. / Changes in permeability caused by connexin 32 mutations underlie X- linked Charcot-Marie-Tooth disease. In: Neuron. 1997 ; Vol. 19, No. 4. pp. 927-938.
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