Regulation of the epithelial sodium channel by membrane trafficking

Abstract

Butterworth MB, Edinger RS, Frizzell RA, Johnson JP. Regulation of the epithelial sodium channel by membrane trafficking.

Aldosterone Regulates MicroRNAs in the Cortical Collecting Duct to Alter Sodium Transport

“…[3][4][5][6][7] Because of its role in the regulation of Na + homeostasis, ENaC has been associated with clinical defects of Na + and water transport. 8 In the kidney, ENaC is localized in principal cells of the distal nephron (distal convoluted tubule and collecting duct), where it participates in final Na + uptake from the luminal urinary space.…”

The Cyp2c44 Epoxygenase Regulates Epithelial Sodium Channel Activity and the Blood Pressure Responses to Increased Dietary Salt

“…Multiple mechanisms are known to participate in the regulation of ENaC activity, including limited proteolysis (30,43,44), hormonal mediated effects on translocation and membrane assembly (9,13,45,46), a serum and glucocorticoid-regulated kinase (SGK-1)-mediated phosphorylation of Nedd4 -2 leading to reduced ubiquitination, retrieval and degradation (17,18,47,48), as well as negative and positive hormonal effects mediated by protein kinases including ERK1/2, protein kinases A and C, and phosphatidylinositol 3-kinase, among others (14 -19, 47-49). Added to the above is the present identification of the Cyp2c44 epoxygenase and its EET metabolites as a new class of in vivo regulators of ENaC activity.…”

Identification of the roles of conserved charged residues in the extracellular domain of an epithelial sodium channel (ENaC) subunit by alanine mutagenesis

“…The route of transport of the subunits apparently proceeds via the Golgi complex and the trans-Golgi network. The proteins are then probably packaged in vesicular endosomes that are directed to the apical membrane (5,36). Studies on a variety of apical proteins have revealed several alternative routes of vesicular trafficking (41).…”

“…Studies on a variety of apical proteins have revealed several alternative routes of vesicular trafficking (41). In some cell types, ENaC appear to be transported in membrane lipid raft domains (5).…”

“…Conserved residues on the surface of ENaC could possibly play a role in the functioning of ENaC, at any level, starting from the trafficking of the subunits to the cell surface (5) and extending up to the process of ion movement within the fully assembled ENaC on the cell surface (22). To examine the significance of these residues, we mutated each to alanine that carries no charge.…”