Syndromic deafness mutations at Asn 14 differentially alter the open stability of Cx26 hemichannels.

ABSTRACT: Connexin 26 (Cx26) is a transmembrane protein that forms hexameric hemichannels that can function when unopposed or dock to form intercellular gap junction channels. Aberrantly functioning unopposed hemichannels are a common feature of syndromic deafness associated with mutations in Cx26. In this study, we examine two different mutations at the same position in the N-terminal domain of Cx26, N14K and N14Y, which have been reported to produce different phenotypes in patients. We find that both N14K and N14Y, when expressed alone or together with wild-type (WT) Cx26, result in functional hemichannels with widely disparate functional properties. N14K currents are robust, whereas N14Y currents are small. The two mutants also exhibit opposite shifts in voltage-dependent loop gating, such that a

SUBMITTER: Sanchez HA 

PROVIDER: S-EPMC4924935 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature