PMID- 16079393
OWN - NLM
STAT- MEDLINE
DCOM- 20060207
LR  - 20231213
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 25
IP  - 31
DP  - 2005 Aug 3
TI  - Prenylation-defective human connexin32 mutants are normally localized and 
      function equivalently to wild-type connexin32 in myelinating Schwann cells.
PG  - 7111-20
AB  - Mutations in GJB1, the gene encoding the gap junction protein connexin32 (Cx32), 
      cause the X-linked form of Charcot-Marie-Tooth disease, an inherited 
      demyelinating neuropathy. The C terminus of human Cx32 contains a putative 
      prenylation motif that is conserved in Cx32 orthologs. Using [3H]mevalonolactone 
      ([3H]MVA) incorporation, we demonstrated that wild-type human connexin32 can be 
      prenylated in COS7 cells, in contrast to disease-associated mutations that are 
      predicted to disrupt the prenylation motif. We generated transgenic mice that 
      express these mutants in myelinating Schwann cells. Male mice expressing a 
      transgene were crossed with female Gjb1-null mice; the male offspring were all 
      Gjb1-null, and one-half were transgene positive; in these mice, all Cx32 was 
      derived from expression of the transgene. The mutant human protein was properly 
      localized in myelinating Schwann cells in multiple transgenic lines and did not 
      alter the localization of other components of paranodes and incisures. Finally, 
      both the C280G and the S281x mutants appeared to "rescue" the phenotype of 
      Gjb1-null mice, because transgene-positive male mice had significantly fewer 
      abnormally myelinated axons than did their transgene-negative male littermates. 
      These results indicate that Cx32 is prenylated, but that prenylation is not 
      required for proper trafficking of Cx32 and perhaps not even for certain aspects 
      of its function, in myelinating Schwann cells.
FAU - Huang, Yan
AU  - Huang Y
AD  - Department of Neurology, The University of Pennsylvania Medical Center, 
      Philadelphia, Pennsylvania 19104, USA. yanhuang@mail.med.upenn.edu
FAU - Sirkowski, Erich E
AU  - Sirkowski EE
FAU - Stickney, John T
AU  - Stickney JT
FAU - Scherer, Steven S
AU  - Scherer SS
LA  - eng
GR  - R01 NS042878/NS/NINDS NIH HHS/United States
GR  - R01 NS42878/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Codon, Terminator)
RN  - 0 (Connexins)
RN  - 452VLY9402 (Serine)
RN  - 9007-49-2 (DNA)
RN  - K848JZ4886 (Cysteine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Amino Acid Motifs/genetics
MH  - Animals
MH  - Codon, Terminator
MH  - Connexins/deficiency/*genetics/metabolism/*physiology
MH  - Conserved Sequence
MH  - Cysteine
MH  - DNA/metabolism
MH  - Evolution, Molecular
MH  - Female
MH  - Femoral Nerve/physiology
MH  - Glycine
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - *Mutation
MH  - Myelin Sheath/*physiology
MH  - Phenotype
MH  - Protein Prenylation/*genetics
MH  - Schwann Cells/*physiology
MH  - Sciatic Nerve/physiology
MH  - Serine
MH  - Tissue Distribution
MH  - Gap Junction beta-1 Protein
PMC - PMC6725241
EDAT- 2005/08/05 09:00
MHDA- 2006/02/08 09:00
PMCR- 2006/02/03
CRDT- 2005/08/05 09:00
PHST- 2005/08/05 09:00 [pubmed]
PHST- 2006/02/08 09:00 [medline]
PHST- 2005/08/05 09:00 [entrez]
PHST- 2006/02/03 00:00 [pmc-release]
AID - 25/31/7111 [pii]
AID - 10.1523/JNEUROSCI.1319-05.2005 [doi]
PST - ppublish
SO  - J Neurosci. 2005 Aug 3;25(31):7111-20. doi: 10.1523/JNEUROSCI.1319-05.2005.