Molecular interaction of connexin 30.3 and connexin 31 suggests a dominant-negative mechanism associated with erythrokeratodermia variabilis

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Serval ID
serval:BIB_1DF339B7F1E8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Molecular interaction of connexin 30.3 and connexin 31 suggests a dominant-negative mechanism associated with erythrokeratodermia variabilis
Journal
Human Molecular Genetics
Author(s)
Plantard  L., Huber  M., Macari  F., Meda  P., Hohl  D.
ISSN
0964-6906 (Print)
Publication state
Published
Issued date
12/2003
Volume
12
Number
24
Pages
3287-94
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Dec 15
Abstract
Connexins are homologous four-transmembrane-domain proteins and major components of gap junctions. We recently identified mutations in either GJB3 or GJB4 genes, encoding respectively connexin 31 (Cx31) or 30.3 (Cx30.3), as causally involved in erythrokeratodermia variabilis (EKV), a mostly autosomal dominant disorder of keratinization. Despite slight differences, phenotypes of EKV Mendes Da Costa (Cx31) and EKV Cram-Mevorah (Cx30.3) show major clinical overlap and both Cx30.3 and Cx31 are expressed in the upper epidermal layers. These similarities suggested to us that Cx30.3 and Cx31 may interact at a molecular level. Indeed, expression of wild-type Cx30.3 in HeLa cell resulted only in minor amounts of protein addressed to the plasma membrane. Mutant Cx30.3 was hardly detectable and disturbed intercellular coupling. In sharp contrast, co-expression of both wild-type proteins led to a gigantic increase of stabilized heteromeric gap junctions. Furthermore, co-expressed wild-type Cx30.3 and Cx31 coprecipitate, which demonstrates a physical interaction. Inhibitor experiments revealed that this interaction begins in the endoplasmic reticulum. These results not only provide new insights into epidermal connexin synthesis and polymerization, but also allow a novel molecular explanation for the similarity of EKV phenotypes.
Keywords
Cell Line Connexins/*genetics/metabolism Gap Junctions/genetics Genes, Dominant Hela Cells Humans Keratosis/*genetics Mutation Skin Diseases, Genetic/*genetics
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 17:36
Last modification date
25/09/2019 7:08
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