Authors: ChingChyuan Su ShuanYow Li YungChang Yen JhihHao Nian WeiGuang Liang JiannJou Yang
Publish Date: 2012/11/22
Volume: 66, Issue: 2, Pages: 277-286
Abstract
Connexins CXs as a component of gap junction channel are homologous four transmembranedomain proteins with numerous studies confirming their auditory functions Among a cohort of patients having incurred nonsyndromic hearing loss we identified two novel missense mutations pR15G and pL23H in the GJC3 gene encoding CX302/CX313 as causally related to hearing loss in previous study However the functional alteration of CX302/CX313 caused by the mutant GJC3 gene remains unknown In this study we compared the intracellular distribution of mutant CX302/CX313 pR15G and pL23H with the wildtype WT protein in HeLa cells and the effect of the mutant protein had on those cells Analytical results indicated that pR15G and pL23H mutant exhibited continuous staining along apposed cell membranes in the fluorescent localization assay which is the same with the WT Moreover ATP release hemichannel function is less in HeLa cells carrying mutant GJC3 genes than those of WT expressing cells We believe that although pR15G and pL23H mutants do not decrease the trafficking of CX proteins mutations in GJC3 genes result in a loss of hemichannel function of CX302/CX313 protein possibly causing hearing loss Results of this study provide a novel molecular explanation for the role of GJC3 in hearing loss
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