Roles of connexins and pannexins in digestive homeostasis

Abstract

Connexin proteins are abundantly present in the digestive system. They primarily form gap junctions, which control the intercellular exchange of critical homeostasis regulators. By doing so, gap junctions drive a plethora of gastrointestinal and hepatic functional features, including gastric and gut motility, gastric acid secretion, intestinal innate immune defense, xenobiotic biotransformation, glycogenolysis, bile secretion, ammonia detoxification and plasma protein synthesis. In the last decade, it has become clear that connexin hemichannels, which are the structural precursors of gap junctions, also provide a pathway for cellular communication, namely between the cytosol and the extracellular environment. Although merely pathological functions have been described, some physiological roles have been attributed to connexin hemichannels, in particular in the modulation of colonic motility. This equally holds true for cellular channels composed of pannexins, connexin-like proteins recently identified in the intestine and the liver, which have become acknowledged key players in inflammatory processes and that have been proposed to control colonic motility, secretion and blood flow.

Fig. 1

a Architecture of connexin and pannexin channels. Gap junctions are formed by the interaction between 2 hemichannels of adjacent cells and mediate intercellular communication (red arrow). Connexin hemichannels and pannexin channels are built up by 6 connexin proteins (green) and 6 pannexin proteins (blue), respectively, and support paracrine communication (purple). b Topology of connexin and pannexin proteins. Connexins (green) and pannexins (blue) all consist of 4 transmembrane domains (TM), 2 extracellular loops (EL), 1 cytoplasmic loop (CL), 1 cytoplasmic carboxy tail (CT) and cytoplasmic amino tail (NT). In comparison with connexins, pannexins have longer EL and CT areas