Spatio-temporal regulation of connexin43 phosphorylation and gap junction dynamics

摘要

Abstract Gap junctions are specialized membrane domains containing tens to thousands of intercellular channels. These channels permit exchange of small molecules ( 3 ) between cells. The common reductionist view of these structures is that they are composed entirely of integral membrane proteins encoded by the 21 member connexin human gene family. However, it is clear that the normal physiological function of this structure requires interaction and regulation by a variety of proteins, especially kinases. Phosphorylation is capable of directly modulating connexin channel function but the most dramatic effects on gap junction activity occur via the organization of the gap junction structures themselves. This is a direct result of the short half-life of the primary gap junction protein, connexin, which requires them to be constantly assembled, remodeled and turned over. The biological consequences of this remodeling are well illustrated during cardiac ischemia, a process wherein gap junctions are disassembled and remodeled resulting in arrhythmia and ultimately heart failure. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve. Highlights ? Gap junctions, composed of connexin proteins, allow for intercellular communication. ? The life cycle of connexin43 (Cx43), the major gap junction protein, is highly regulated. ? Through direct phosphorylation of Cx43, kinases regulate gap junctional communication. ? Cx43 phosphorylation is critical during epidermal wounding and cardiac ischemia.