COMMD10 Regulates Endosomal Recycling of Epithelial Sodium Channel (ENaC)

Abstract

SummaryThe epithelial sodium channel (ENaC) plays an essential role in the regulation of sodium transport in distal nephron. ENaC cell surface population of renal principal cells is tightly regulated by hormones such as aldosterone and vasopressin through protein trafficking pathways that translocate ENaC to and from the cell surface. Internalized ENaC from the plasma membrane follows the degradative pathway promoted by ubiquitin fusion or the recycling pathway after deubiquitination and sorting on early endosomes. The mechanism by which ENaC is recycled back to the plasma membrane through regulated recycling is less known. Here, we show that regulated recycling of ENaC is strictly dependent on COMMD10 and localization pattern of COMMD10 on Rab5, −7, and −11 vesicles is similar to that of WASH and Arp2/3. Furthermore, here we report that COMMD1 and −10 protein levels are regulated by aldosterone and calcium. This study proposes that for regulated recycling of ENaC, conventional endosomal sorting and recycling complexes such as CCC complex are recruited.HighlightsCOMMD10 alters ENaC cell surface population through the regulated recycling pathway. COMMD10 localizes on Rab5-, Rab7-, and Rab11-positive endosomes in a similar pattern as endosomal actin polymerization complexes WASH and Arp2/3. Aldosterone downregulates COMMD1 and −10 protein levels while calcium upregulates COMMD10 protein level.Graphical Abstract