PMID- 9592087
OWN - NLM
STAT- MEDLINE
DCOM- 19980604
LR  - 20231213
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 18
IP  - 11
DP  - 1998 Jun 1
TI  - Connexin32 mutations associated with X-linked Charcot-Marie-Tooth disease show 
      two distinct behaviors: loss of function and altered gating properties.
PG  - 4063-75
AB  - The X-linked form of Charcot-Marie-Tooth disease (CMTX) is associated with 
      mutations in the gene encoding connexin32 (Cx32), which is expressed in Schwann 
      cells. We have compared the functional properties of 11 Cx32 mutations with those 
      of the wild-type protein by testing their ability to form intercellular channels 
      in the paired oocyte expression system. Although seven mutations were 
      functionally incompetent, four others were able to generate intercellular 
      currents of the same order of magnitude as those induced by wild-type Cx32 
      (Cx32wt). In homotypic oocyte pairs, CMTX mutations retaining functional activity 
      induced the development of junctional currents that exhibited changes in the 
      sensitivity and kinetics of voltage dependence with respect to that of Cx32wt. 
      The four mutations were also capable of interacting in heterotypic configuration 
      with the wild-type protein, and in one case the result was a marked rectification 
      of junctional currents in response to voltage steps of opposite polarity. In 
      addition, the functional CMTX mutations displayed the same selective pattern of 
      compatibility as Cx32wt, interacting with Cx26, Cx46, and Cx50 but failing to do 
      so with Cx40. Although the functional mutations exhibited sensitivity to 
      cytoplasmic acidification, which induced a >/=80% decrease in junctional 
      currents, both the rate and extent of channel closure were enhanced markedly for 
      two of them. Together, these results indicate that the functional consequences of 
      CMTX mutations of Cx32 are of two drastically distinct kinds. The presence of a 
      functional group of mutations suggests that a selective deficit of Cx32 channels 
      may be sufficient to impair the homeostasis of Schwann cells and lead to the 
      development of CMTX.
FAU - Ressot, C
AU  - Ressot C
AD  - Unite de Neurovirologie et Regeneration du Systeme Nerveux, Institut Pasteur, 
      F-75724 Paris Cedex 15, France.
FAU - Gomes, D
AU  - Gomes D
FAU - Dautigny, A
AU  - Dautigny A
FAU - Pham-Dinh, D
AU  - Pham-Dinh D
FAU - Bruzzone, R
AU  - Bruzzone R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Connexins)
RN  - 0 (GJB2 protein, human)
RN  - 127120-53-0 (Connexin 26)
SB  - IM
MH  - Animals
MH  - Charcot-Marie-Tooth Disease/*genetics
MH  - Connexin 26
MH  - Connexins/chemistry/*genetics
MH  - Electric Stimulation
MH  - Gap Junctions/chemistry/physiology
MH  - Genetic Linkage
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Ion Channel Gating/*genetics
MH  - Mutagenesis/physiology
MH  - Mutation/physiology
MH  - Myelin Sheath/chemistry/physiology
MH  - Oocytes/physiology
MH  - Phenotype
MH  - Protein Structure, Tertiary
MH  - Schwann Cells/physiology
MH  - *X Chromosome
MH  - Xenopus
MH  - Gap Junction beta-1 Protein
PMC - PMC6792797
EDAT- 1998/06/06 00:00
MHDA- 1998/06/06 00:01
PMCR- 1998/12/01
CRDT- 1998/06/06 00:00
PHST- 1998/06/06 00:00 [pubmed]
PHST- 1998/06/06 00:01 [medline]
PHST- 1998/06/06 00:00 [entrez]
PHST- 1998/12/01 00:00 [pmc-release]
AID - 2054 [pii]
AID - 10.1523/JNEUROSCI.18-11-04063.1998 [doi]
PST - ppublish
SO  - J Neurosci. 1998 Jun 1;18(11):4063-75. doi: 10.1523/JNEUROSCI.18-11-04063.1998.