Severe neuropathy with leaky connexin32 hemichannels - CMTX

[Guest guest]

Ann Neurol. 2005 Apr 25;57(5):749-754

Severe neuropathy with leaky connexin32 hemichannels.

Liang GS, de M, Gomez- JM, Glass JD, Scherer SS,

Mintz M, Barrio LC, Fischbeck KH.

Department of Neurology, Parkinson's Disease and Movement Disorders

Center, Department of Neurology, Penn Neurological Institute,

University of Pennsylvania Medical Center, Philadelphia, PA.

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.