Connexins are homologous four-transmembrane-domain proteins and major components of gap junctions. We recently identified mutations in either @entity6360 or @entity64033 genes, encoding respectively @entity6360 ( @entity6360 ) or 30.3 ( @entity4700 .3), as causally involved in @entity57969 ( @entity57969 ), a mostly @entity74 . Despite slight differences, phenotypes of @entity57969 Mendes Da Costa ( @entity6360 ) and @entity57969 Cram-Mevorah ( @entity4700 .3) show major clinical overlap and both @entity4700 .3 and @entity6360 are expressed in the upper epidermal layers. These similarities suggested to us that @entity4700 .3 and @entity6360 may interact at a molecular level. Indeed, expression of wild-type @entity4700 .3 in HeLa cell resulted only in minor amounts of protein addressed to the plasma membrane. Mutant @entity4700 .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 @entity4700 .3 and @entity6360 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 @entity57969 phenotypes.

Molecular interaction of XXXX and @entity6360 suggests a dominant-negative mechanism associated with @entity57969 .

@entity74 :: ('MESH:D030342', 'Disease') :: ['autosomal dominant disorder of keratinization'] @entity6360 :: ('2707', 'Gene') :: ['GJB3', 'connexin 31', 'Cx31'] @entity64033 :: ('127534', 'Gene') :: ['GJB4'] @entity57969 :: ('MESH:D056266', 'Disease') :: ['erythrokeratodermia variabilis', 'EKV'] @entity4700 :: ('10804', 'Gene') :: ['Cx30']
@entity64033 :: (127534,Gene) :: ['connexin 30.3']
