PMID- 10848620
OWN - NLM
STAT- MEDLINE
DCOM- 20000825
LR  - 20231213
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 11
IP  - 6
DP  - 2000 Jun
TI  - Intracellular transport, assembly, and degradation of wild-type and 
      disease-linked mutant gap junction proteins.
PG  - 1933-46
AB  - More than 130 different mutations in the gap junction integral plasma membrane 
      protein connexin32 (Cx32) have been linked to the human peripheral neuropathy 
      X-linked Charcot-Marie-Tooth disease (CMTX). How these various mutants are 
      processed by the cell and the mechanism(s) by which they cause CMTX are unknown. 
      To address these issues, we have studied the intracellular transport, assembly, 
      and degradation of three CMTX-linked Cx32 mutants stably expressed in PC12 cells. 
      Each mutant had a distinct fate: E208K Cx32 appeared to be retained in the 
      endoplasmic reticulum (ER), whereas both the E186K and R142W mutants were 
      transported to perinuclear compartments from which they trafficked either to 
      lysosomes (R142W Cx32) or back to the ER (E186K Cx32). Despite these differences, 
      each mutant was soluble in nonionic detergent but unable to assemble into 
      homomeric connexons. Degradation of both mutant and wild-type connexins was rapid 
      (t(1/2) < 3 h) and took place at least in part in the ER by a process sensitive 
      to proteasome inhibitors. The mutants studied are therefore unlikely to cause 
      disease by accumulating in degradation-resistant aggregates but instead are 
      efficiently cleared from the cell by quality control processes that prevent 
      abnormal connexin molecules from traversing the secretory pathway.
FAU - VanSlyke, J K
AU  - VanSlyke JK
AD  - Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences 
      University, Portland, Oregon 97201, USA.
FAU - Deschenes, S M
AU  - Deschenes SM
FAU - Musil, L S
AU  - Musil LS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Connexins)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - Biological Transport, Active
MH  - Charcot-Marie-Tooth Disease/*genetics
MH  - Connexins/*genetics/*metabolism
MH  - Humans
MH  - Intracellular Fluid/metabolism
MH  - PC12 Cells
MH  - *Point Mutation
MH  - Rats
MH  - Transfection
MH  - Gap Junction beta-1 Protein
PMC - PMC14894
EDAT- 2000/06/10 09:00
MHDA- 2000/09/02 11:01
CRDT- 2000/06/10 09:00
PHST- 2000/06/10 09:00 [pubmed]
PHST- 2000/09/02 11:01 [medline]
PHST- 2000/06/10 09:00 [entrez]
AID - 1213 [pii]
AID - 10.1091/mbc.11.6.1933 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2000 Jun;11(6):1933-46. doi: 10.1091/mbc.11.6.1933.