title: COMMD1 regulates the delta epithelial sodium channel (δENaC) through trafficking and ubiquitination.
abstract: The delta subunit of the epithelial sodium channel (δENaC) is a member of the ENaC/degenerin family of ion channels. δENaC is distinct from the related α-, β- and γENaC subunits, known for their role in sodium homeostasis and blood pressure control, as δENaC is expressed in brain neurons and activated by external protons. COMMD1 (copper metabolism Murr1 domain 1) was previously found to associate with and downregulate δENaC activity. Here, we show that COMMD1 interacts with δENaC through its COMM domain. Co-expression of δENaC with COMMD1 significantly reduced δENaC surface expression, and led to an increase in δENaC ubiquitination. Immunocytochemical and confocal microscopy studies show that COMMD1 promoted localization of δENaC to the early/recycling endosomal pool where the two proteins were localized together. These results suggest that COMMD1 downregulates δENaC activity by reducing δENaC surface expression through promoting internalization of surface δENaC to an intracellular recycling pool, possibly via enhanced ubiquitination.
authors: Department of Physiology, University of Otago, PO Box 913, Dunedin 9054, New Zealand.
authors: Tina
authors: T
authors: Chang
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; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C480519:COMMD1 protein, human; D002352:Carrier Proteins; D053503:Epithelial Sodium Channels