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Severe neuropathy with leaky connexin32 hemichannels
Author(s) -
Liang Grace S. Lin,
de Miguel Marta,
GómezHernández Juan M.,
Glass Jonathan D.,
Scherer Steven S.,
Mintz Mark,
Barrio Luis C.,
Fischbeck Kenneth H.
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20459
Subject(s) - connexin , missense mutation , gap junction , connexin 32 , mutation , mutant , microbiology and biotechnology , biology , medicine , genetics , gene , intracellular
X‐linked Charcot‐Marie‐Tooth disease is one of a set of diseases caused by mutations in gap junction proteins called connexins. We identified a connexin32 missense mutation (F235C) in a girl with unusually severe neuropathy. The localization and trafficking of the mutant protein in cell culture was normal, but electrophysiological studies showed that the mutation caused abnormal hemichannel opening, with excessive permeability of the plasma membrane and decreased cell survival. Abnormal leakiness of connexin hemichannels is likely a mechanism of cellular toxicity in this and perhaps other diseases caused by connexin mutations. Ann Neurol 2005;57:749–754