2014
DOI: 10.1152/ajpcell.00098.2013
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Functional effects of Cx50 mutations associated with congenital cataracts

Abstract: Mutations in connexin50 (Cx50) cause dominant cataracts in both humans and mice. The exact mechanisms by which mutations cause these variable phenotypes are poorly understood. We have examined the functional properties of gap junctions made by three Cx50 mutations, V44E, D47N, and V79L, expressed in mammalian cell lines. V44E trafficked to the plasma membrane properly and formed gap junctional plaques. However, the mutant did not form functional gap junctions when expressed alone, or with wild-type (WT) Cx46 a… Show more

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Cited by 31 publications
(33 citation statements)
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“…However, in the current study the cholesterol distribution into lipoprotein classes was modulated by distinct connexin 50 genotype, perhaps through non-genomic action of the glucocorticoid similar to the one described for Cx43 [35]. It is probable that the mutant Cx50 cannot form hemichannels or gap junctions in SHR- Dca −/− tissues [36] and their function related to lipid handling is compensated for by other members of the connexin family. However, in heterozygous animals, formation of heteromeric hemichannels containing both wild type and mutant Cx50 is possible with functional consequences (distinct permeability, voltage gating, ability to form homotypic or heterotypic gap junctions) leading, through yet unidentified mechanism, to the observed hyperlipidemia.…”
Section: Discussionmentioning
confidence: 66%
“…However, in the current study the cholesterol distribution into lipoprotein classes was modulated by distinct connexin 50 genotype, perhaps through non-genomic action of the glucocorticoid similar to the one described for Cx43 [35]. It is probable that the mutant Cx50 cannot form hemichannels or gap junctions in SHR- Dca −/− tissues [36] and their function related to lipid handling is compensated for by other members of the connexin family. However, in heterozygous animals, formation of heteromeric hemichannels containing both wild type and mutant Cx50 is possible with functional consequences (distinct permeability, voltage gating, ability to form homotypic or heterotypic gap junctions) leading, through yet unidentified mechanism, to the observed hyperlipidemia.…”
Section: Discussionmentioning
confidence: 66%
“…Also, since this is a dominant disease, it would be really interesting to assess whether the mutant protein dimerize with the wild-type form would impede the proper localization or function of the wild-type [44], which would help to design possible genetic therapies in the future.…”
Section: Discussionmentioning
confidence: 99%
“…Four other mutations, p.Val79Leu, p.Pro88Ser, p.Pro88Gln, and p.Pro88Thr, have previously been localized to the second transmembrane domain (Additional file 5). Functional expression studies of the relatively conservative p.Val79Leu substitution results in functional gap-junction channels with altered voltage-gating and a reduction in the single-channel open probability [28]. By contrast, neither of the non-conservative p.Pro88Gln and p.Pro88Ser substitutions was targeted to the plasma membrane, with the former accumulating in the endoplasmic-reticulum (ER)-Golgi-complex and the latter forming discrete cytoplasmic inclusions [26].…”
Section: Discussionmentioning
confidence: 99%