title: Functional interaction of COMMD3 and COMMD9 with the epithelial sodium channel.
abstract: The epithelial sodium channel (ENaC) plays an important role in controlling Na⁺ homeostasis, extracellular fluid volume, and blood pressure. Copper metabolism Murr1 domain-containing protein 1 (COMMD1) interacts with ENaC and downregulates ENaC. COMMD1 belongs to the COMMD family consisting of COMMD1-10, and all COMMD family members share a C-terminal COMM domain. Here, we report that COMMD2-10 also interacts with ENaC, and COMMD3 and COMMD9 were selected for further study. Amiloride-sensitive current in mammalian epithelia expressing ENaC was significantly reduced by COMMD3 or COMMD9, and ENaC expression at the cell surface was significantly decreased in the presence of COMMD3 or COMMD9. COMMD3 and COMMD9 retained their ability to reduce current when COMMD1 was knocked down. COMMD3 and COMMD9 were widely expressed in kidney and were colocalized with ENaC in renal collecting duct cells. These data suggest that COMMD3 and COMMD9 may be endogenous regulators of ENaC to regulate Na⁺ transport through altering ENaC cell surface expression.
authors: Department of Physiology, University of Otago, Dunedin, New Zealand.
authors: Yong Feng
authors: YF
authors: Liu
authors: Marianne
authors: M
authors: Swart
authors: Ying
authors: Y
authors: Ke
authors: Kevin
authors: K
authors: Ly
authors: Fiona J
authors: FJ
authors: McDonald
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D021122:Protein Subunits; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C583282:COMMD3 protein, rat; C583283:COMMD9 protein, rat; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D021122:Protein Subunits; D000584:Amiloride; D012964:Sodium
keywords: ENaC; amiloride; kidney