Membrane trafficking pathways regulating the epithelial Na+ channel

摘要

In this review, we focus on the cellular trafficking of the epithelial Na+ channel (ENaC), which is composed of a-, (3-, and 7-subunits, that, together, form a channel responsible for Na+ reabsorption at the apical membrane of a number of epithelia including the distal kidney, lung, and distal colon. ENaC subunits are members of the larger ENaC/degenerin (DEG) family of ion channels that includes ENaC and acid-sensing ion channel subunits in mammals and related ENaC paralogs identified across the vertebrate taxa (for a review, see Ref. 60). More distantly related subunits appear in lower organisms such as mechanosensory protein (MEC) and DEG proteins in Caenorhabditis elegans (for a review, see Ref. 74). Each of the a-, |3-, and 7-subunits of ENaC contain short cytosolic NH2- and COOH-terminal domains available for interacting with intracellular proteins, two membrane-spanning domains that contribute to the formation of a Na+-conducting pore, and a large glycosylated extracellular loop (27). Recently, the three-dimensonal structure of af ENaC was resolved using cryoelectron microscopy (108), confirming that these subunits associate to form a trimer, although the cytosolic domains had to be removed to produce a complex amenable to structural determination. ENaC sub-units are present in many cell types throughout the body, including the salivary and sweat glands, lungs, distal colon, and kidneys (58). In the late distal tubule and collecting duct of the kidney, regulation of Na+ reabsorption through ENaC