Adenosine-triphosphate-sensitive K+channel (Kir6.1): A novel phosphospecific interaction partner of connexin 43 (Cx43)

Connexin 43 (Cx43) is a phosphoprotein expressed in a wide variety of cells. Cx43 and adenosine-triphosphate-sensitive K+channels [K+(ATP)] are part of same signaling pathway that regulates cell survival during stress and ischemia preconditioning. Molecular mechanism for their coordinated role in ischemia/hypoxia preconditioning is not well known. Using pull down, co-immunoprecipitation assays and co-localization studies we provide evidence, for the first time that Kir6.1, a K+(ATP) channel protein component, can interact with Cx43. Further we show that the interaction was phospho-specific such that Cx43 phosphorylated at serine 262 (S262) interacted with Kir6.1 in preference to the unphosphorylated form of Cx43. Introduction of phospho-deficient mutation at serine 262 (S262A) in Cx43 completely abolished the interaction. Our data provide an interesting lead about a possible partnership between Cx43 and Kir6.1, which will help in better understanding their role in ischemia/hypoxia preconditioning.

► Adenosine-triphosphate-sensitive K+channels [K+(ATP)] is the novel interaction partner of connexin 43 (Cx43).
► Serine 262 (S262) of the Cx43 is indispensible for this interaction.
► Phosphorylation of serine 262 is critical for the interaction of Cx43 with K+(ATP).