PMID- 10646523
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 74
IP  - 2
DP  - 2000 Feb
TI  - Analysis of gap junction assembly using mutated connexins detected in
      Charcot-Marie-Tooth X-linked disease.
PG  - 711-20
AB  - The assembly of gap junction intercellular communication channels was studied by 
      analysis of the molecular basis of the dysfunction of connexin 32 mutations
      associated with the X-linked form of Charcot-Marie-Tooth disease in which
      peripheral nervous transmission is impaired. A cell-free translation system
      showed that six recombinant connexin 32 mutated proteins-four point mutations at 
      the cytoplasmic amino terminus, one at the membrane aspect of the cytoplasmic
      carboxyl terminus, and a deletion in the intracellular loop-were inserted into
      microsomal membranes and oligomerised into connexon hemichannels with varying
      efficiencies. The functionality of the connexons was determined by the ability of
      HeLa cells expressing the respective connexin cDNAs to transfer Lucifer yellow.
      The intracellular trafficking properties of the mutated connexins were determined
      by immunocytochemistry. The results show a relationship between intracellular
      interruption of connexin trafficking, the efficiency of intercellular
      communication, and the severity of the disease phenotype. Intracellular retention
      was explained either by deficiencies in the ability of connexins to oligomerise
      or by mutational changes at two targeting motifs. The results point to dominance 
      of two specific targeting motifs: one at the amino terminus and one at the
      membrane aspect of the cytoplasmically located carboxyl tail. An intracellular
      loop deletion of six amino acids, associated with a mild phenotype, showed
      partial oligomerisation and low intercellular dye transfer compared with
      wild-type connexin 32. The results show that modifications in trafficking and
      assembly of gap junction channels emerge as a major feature of
      Charcot-Marie-Tooth X-linked disease.
FAU - Martin, P E
AU  - Martin PE
AD  - Department of Medical Biochemistry, University of Wales College of Medicine,
      Cardiff, UK. wmbpem@cardiff.ac.uk
FAU - Mambetisaeva, E T
AU  - Mambetisaeva ET
FAU - Archer, D A
AU  - Archer DA
FAU - George, C H
AU  - George CH
FAU - Evans, W H
AU  - Evans WH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Connexins)
RN  - 0 (connexin 32)
SB  - IM
MH  - Animals
MH  - COS Cells/metabolism/physiology
MH  - Cell-Free System
MH  - Charcot-Marie-Tooth Disease/*genetics
MH  - Connexins/chemistry/*genetics/metabolism
MH  - Gap Junctions/*physiology
MH  - *Genetic Linkage
MH  - Humans
MH  - Mutation/*physiology
MH  - Phenotype
MH  - Protein Processing, Post-Translational
MH  - *X Chromosome
EDAT- 2000/01/26 00:00
MHDA- 2000/01/26 00:01
CRDT- 2000/01/26 00:00
PHST- 2000/01/26 00:00 [pubmed]
PHST- 2000/01/26 00:01 [medline]
PHST- 2000/01/26 00:00 [entrez]
AID - 10.1046/j.1471-4159.2000.740711.x [doi]
PST - ppublish
SO  - J Neurochem. 2000 Feb;74(2):711-20. doi: 10.1046/j.1471-4159.2000.740711.x.