PMID- 21280457
OWN - NLM
STAT- MEDLINE
DCOM- 20110308
LR  - 20191112
IS  - 0334-1763 (Print)
IS  - 0334-1763 (Linking)
VI  - 21
IP  - 5
DP  - 2010
TI  - Gap junction disorders of myelinating cells.
PG  - 397-419
AB  - Gap junctions (GJs) are channels that allow the diffusion of ions and small 
      molecules across apposed cell membranes. In peripheral nerves, Schwann cells 
      express the GJ proteins connexin32 (Cx32) and Cx29, which have distinct 
      localizations. Cx32 forms GJs through non-compact myelin areas, whereas Cx29 
      forms hemichannels in the innermost layers of myelin apposing axonal Shaker-type 
      K+ channels. In the CNS, rodent oligodendrocytes express Cx47, Cx32 and Cx29. 
      Cx47 is expressed by all types of oligodendrocytes both in the white and grey 
      matter and forms GJs on cell bodies and proximal processes, as well as most of 
      the intercellular channels with astrocytes. Cx32 is expressed mostly by white 
      matter oligodendrocytes and is localized in the myelin sheath of large diameter 
      fibers. Cx29, and its human ortholog Cx31.3, appear to be restricted to 
      oligodendrocytes that myelinate small caliber fibers, likely forming 
      hemichannels. The importance of intercellular and intracellular GJs in 
      myelinating cells are demonstrated by human disorders resulting from mutations 
      affecting GJ proteins. The X-linked Charcot Marie Tooth disease (CMT1X) is caused 
      by hundreds of mutations affecting Cx32. Patients with CMT1X present mainly with 
      a progressive peripheral neuropathy, which may be accompanied by CNS myelin 
      dysfunction. Mutations in Cx47 may cause a devastating leukodystrophy called 
      Pelizaeus-Merzbacher-like disease or a milder spastic paraplegia. In addition, 
      CNS demyelination may be caused by defects in genes expressing astrocytic GJ 
      proteins, which are essential for oligodendrocytes. Findings from in vitro and in 
      vivo models of these disorders developed over the last decade indicate that most 
      mutations cause loss of function and an inability of the mutant connexins to form 
      functional GJs. Here we review the clinical, genetic, and neurobiological aspects 
      of GJ disorders affecting the PNS and CNS myelinating cells.
FAU - Kleopa, Kleopas A
AU  - Kleopa KA
AD  - Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics, Nicosia, 
      Cyprus. kleopa@cing.ac.cy
FAU - Orthmann-Murphy, Jennifer
AU  - Orthmann-Murphy J
FAU - Sargiannidou, Irene
AU  - Sargiannidou I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Germany
TA  - Rev Neurosci
JT  - Reviews in the neurosciences
JID - 8711016
RN  - 0 (Connexins)
SB  - IM
MH  - Animals
MH  - Connexins/genetics/metabolism
MH  - Gap Junctions/genetics/metabolism/*pathology
MH  - Humans
MH  - Models, Biological
MH  - Models, Molecular
MH  - Mutation/genetics
MH  - Myelin Sheath/*metabolism
MH  - Nervous System Diseases/genetics/metabolism/*pathology
MH  - *Schwann Cells
EDAT- 2011/02/02 06:00
MHDA- 2011/03/09 06:00
CRDT- 2011/02/02 06:00
PHST- 2011/02/02 06:00 [entrez]
PHST- 2011/02/02 06:00 [pubmed]
PHST- 2011/03/09 06:00 [medline]
AID - 10.1515/revneuro.2010.21.5.397 [doi]
PST - ppublish
SO  - Rev Neurosci. 2010;21(5):397-419. doi: 10.1515/revneuro.2010.21.5.397.