PMID- 10751670
OWN - NLM
STAT- MEDLINE
DCOM- 20000802
LR  - 20231213
VI  - 32
IP  - 1
DP  - 2000 Apr
TI  - Connexin channels in Schwann cells and the development of the X-linked form of 
      Charcot-Marie-Tooth disease.
PG  - 192-202
AB  - Charcot-Marie-Tooth disease comprises a group of genetically heterogenous 
      disorders of the peripheral nervous system. The X-linked form of 
      Charcot-Marie-Tooth (CMTX) is associated with mutations in the gene encoding the 
      gap junction protein connexin32 (Cx32), which is expressed in Schwann cells. 
      Immunocytochemical evidence suggests that Cx32 is localized to the incisures of 
      Schmidt-Lanterman and the paranodes of myelinating Schwann cells, where it 
      appears to form reflexive gap junctions. It is currently thought that this 
      cytoplasmic continuity provides a much shorter diffusion pathway for the 
      transport of ions, metabolites and second messenger molecules through 
      intracellular channels between the adaxonal and peri-nuclear regions of Schwann 
      cells, across the myelin sheath. This review summarizes our current understanding 
      of the role of connexins in Schwann cells and focuses on the lessons for channel 
      function and disease pathophysiology derived from the functional analysis of Cx32 
      mutations. One of the most intriguing aspects emerging from this work is that 
      several mutations retain functional competence, although the mutated channels 
      exhibit altered gating properties. This suggests that partial and/or selective 
      disruption of the radial communication pathway formed by Cx32 is sufficient to 
      cause a functional deficit and lead to the development of CMTX. The next 
      challenge will be to define, at the molecular level, the sequence of events 
      involved in the disease process. The presence of a group of functional mutations 
      should help understand the cellular basis of CMTX, by allowing the identification 
      of the specific molecules that need to be exchanged through Cx32 channels, but 
      are excluded from the mutated ones.
FAU - Ressot, C
AU  - Ressot C
AD  - Unite de Neurovirologie et Regeneration du Systeme Nerveux, Institut Pasteur, 25, 
      rue du Dr. Roux, F-75724, Paris, France.
FAU - Bruzzone, R
AU  - Bruzzone R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - Brain Res Brain Res Rev
JT  - Brain research. Brain research reviews
JID - 8908638
RN  - 0 (Connexins)
SB  - IM
MH  - Animals
MH  - Charcot-Marie-Tooth Disease/*genetics/*physiopathology
MH  - Connexins/*genetics
MH  - Gap Junctions/chemistry/*physiology
MH  - Genetic Linkage
MH  - Humans
MH  - Mutation
MH  - Schwann Cells/chemistry/*physiology
MH  - *X Chromosome
MH  - Gap Junction beta-1 Protein
RF  - 94
EDAT- 2000/04/07 09:00
MHDA- 2000/08/06 11:00
CRDT- 2000/04/07 09:00
PHST- 2000/04/07 09:00 [pubmed]
PHST- 2000/08/06 11:00 [medline]
PHST- 2000/04/07 09:00 [entrez]
AID - S0165017399000818 [pii]
AID - 10.1016/s0165-0173(99)00081-8 [doi]
PST - ppublish
SO  - Brain Res Brain Res Rev. 2000 Apr;32(1):192-202. doi: 
      10.1016/s0165-0173(99)00081-8.