PMID- 12111842
OWN - NLM
STAT- MEDLINE
DCOM- 20020812
LR  - 20231213
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 68
IP  - 5
DP  - 2002 Jun 1
TI  - Cellular mechanisms of connexin32 mutations associated with CNS manifestations.
PG  - 522-34
AB  - Both oligodendrocytes and myelinating Schwann cells express the gap junction 
      protein connexin32 (Cx32). Mutations in the gene encoding Cx32 (GJB1) cause the 
      X-linked form of Charcot-Marie-Tooth disease (CMTX). Although most CMTX patients 
      do not have clinical central nervous system (CNS) manifestations, subclinical 
      evidence of CNS dysfunction is common. We investigated the cellular effects of a 
      subgroup of GJB1/Cx32 mutations that have been reported to cause clinical CNS 
      dysfunction. We hypothesized that these mutants have dominant-negative effects on 
      other connexins expressed by oligodendrocytes, specifically Cx45. We expressed 
      these and other Cx32 mutants in communication-incompetent as well as 
      Cx45-expressing HeLa cells, and analyzed the transfected cells by 
      immunocytochemistry and immunoblotting. In communication-incompetent cells, the 
      mutants associated with CNS phenotypes failed to reach the cell membrane and were 
      instead retained in the endoplasmic reticulum (A39V, T55I) or Golgi apparatus 
      (M93V, R164Q, R183H), although rare gap junction plaques were found in cells 
      expressing M93V or R183H. In HeLa cells stably expressing Cx45, these Cx32 
      mutants showed a similar expression pattern, and did not alter the pattern of 
      Cx45 expression. These results indicate that Cx32 mutants that are associated 
      with a CNS phenotype do not interact with Cx45, but may instead have other toxic 
      effects in oligodendrocytes.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Kleopa, Kleopas A
AU  - Kleopa KA
AD  - Department of Neurology, University of Pennsylvania School of Medicine, 
      Philadelphia, Pennsylvania, USA. kleopa@mail.med.upenn.edu
FAU - Yum, Sabrina W
AU  - Yum SW
FAU - Scherer, Steven S
AU  - Scherer SS
LA  - eng
GR  - NS08075/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Connexins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (connexin 45)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Cell Communication/genetics
MH  - Charcot-Marie-Tooth Disease/*physiopathology
MH  - Connexins/*genetics/*metabolism
MH  - Cysteine Endopeptidases/metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Gap Junctions/metabolism
MH  - Gene Expression/physiology
MH  - Golgi Apparatus/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Lysosomes/metabolism
MH  - Multienzyme Complexes/metabolism
MH  - Mutagenesis, Site-Directed/physiology
MH  - Oligodendroglia/*physiology
MH  - Phenotype
MH  - Proteasome Endopeptidase Complex
MH  - Protein Transport/physiology
MH  - Schwann Cells/physiology
MH  - Gap Junction beta-1 Protein
EDAT- 2002/07/12 10:00
MHDA- 2002/08/13 10:01
CRDT- 2002/07/12 10:00
PHST- 2002/07/12 10:00 [pubmed]
PHST- 2002/08/13 10:01 [medline]
PHST- 2002/07/12 10:00 [entrez]
AID - 10.1002/jnr.10255 [doi]
PST - ppublish
SO  - J Neurosci Res. 2002 Jun 1;68(5):522-34. doi: 10.1002/jnr.10255.