American Journal of Physiology-Renal Physiology · 2013 · 42 citations · 34 references
Life SciencesCell BiologyPhysiologyGene ExpressionMolecular PhysiologyRenal PathophysiologyCopper MetabolismElectrolyte HomeostasisIon Channel RegulationIon ChannelsRenal PhysiologySodium HomeostasisBlood PressureCollecting Duct PhysiologyCollecting Duct SystemEpithelial Sodium ChannelsRegulatorsSodium Balance RegulationSodium Channel PhysiologySodium Transport Regulation
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.
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Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits
Cecilia M. Canessa, Laurent Schild, Gary Buell et al. · Nature · 1994 · 2K citations