Regulation of connexin43 protein complexes by intracellular acidification.

摘要: Ischemia-induced acidification of astrocytes or cardiac myocytes reduces intercellular communication by closing gap junction channels and subsequently internalizing proteins. To determine whether such coupling changes might be attributable to altered interactions between connexin43 (Cx43) other proteins, we applied the nigericin/high K + method vary intracellular pH (pHi) in cultured cortical astrocytes. Intracellular was accompanied internalization Cx43 with retention scaffolding protein Zonula Occludens-1 (ZO-1) at cell surfaces, suggesting that ZO-1 dissociate low pHi. Coimmunoprecipitation studies revealed decreased binding increased c-Src Resonant mirror spectroscopy used quantify SH3 domain PDZ domains carboxyl terminal (Cx43CT). Data indicate c-Src/Cx43CT interaction is highly dependent whereas ZO-1/Cx43CT not. Moreover, Cx43CT prevented reversed binding. We hypothesize affinity for pHi aids separation from this may facilitate Cx43. These data suggest protracted remodel protein-protein involving thus provide an important protective mechanism limit lesion spread after ischemic injury.