Cataract-associated connexin 46 mutation alters its interaction with calmodulin and function of hemichannels.

ABSTRACT: Connexin channels help maintain eye lens homeostasis and transparency. The G143R missense substitution in connexin (Cx) 46 is associated with congenital Coppock cataracts; however, the underlying molecular mechanism is largely unknown. Here, we report that compared with WT Cx46, the G143R substitution abolishes hemichannel conductance in Xenopus oocytes and in HeLa cells. Moreover, this substitution is dominant-negative and inhibits conductance of WT Cx46. CD analysis indicated that the substitution greatly reduces the α-helical structure of the intracellular Cx46 loop domain. Protein pulldown assays and isothermal titration calorimetry revealed that this Cx46 domain directly interacts with calmodulin (CaM) in a Ca²⁺-dependent fashion, an observation confirmed by immunofl

SUBMITTER: Hu Z 

PROVIDER: S-EPMC5818178 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature