Roles of the C termini of α-, β-, and γ-subunits of epithelial Na⁺ channels (ENaC) in regulating ENaC and mediating its inhibition by cytosolic Na⁺

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dc.contributor.authorDinudom, A.
dc.contributor.authorHarvey, K.
dc.contributor.authorKomwatanat, P.
dc.contributor.authorJolliffe, C.
dc.contributor.authorYoung, J.
dc.contributor.authorKumar, S.
dc.contributor.authorCook, D.
dc.date.issued2001
dc.description.abstractThe amiloride-sensitive epithelial Na+ channels (ENaC) in the intralobular duct cells of mouse mandibular glands are inhibited by the ubiquitin-protein ligase, Nedd4, which is activated by increased intracellular Na+. In this study we have used whole-cell patch clamp methods in mouse mandibular duct cells to investigate the role of the C termini of the α-, β-, and γ-subunits of ENaC in mediating this inhibition. We found that peptides corresponding to the C termini of the β- and γ-subunits, but not the α-subunit, inhibited the activity of the Na+ channels. This mechanism did not involve Nedd4 and probably resulted from the exogenous C termini interfering competitively with the protein-protein interactions that keep the channels active. In the case of the C terminus of mouse β-ENaC, the interacting motif included βSer631, βAsp632, and βSer633. In the C terminus of mouse γ-ENaC, it included γSer640. Once these motifs were deleted, we were able to use the C termini of β- and γ-ENaC to prevent Nedd4-mediated down-regulation of Na+ channel activity. The C terminus of the α-subunit, on the contrary, did not prevent Nedd4-mediated inhibition of the Na+ channels. We conclude that mouse Nedd4 interacts with the β- and γ-subunits of ENaC.
dc.description.statementofresponsibilityAnuwat Dinudom,Kieran F. Harvey,Permsak Komwatana,Corina N. Jolliffe,John A. Young,Sharad Kumar,and David I. Cook
dc.identifier.citationJournal of Biological Chemistry, 2001; 276(17):13744-13749
dc.identifier.doi10.1074/jbc.M011273200
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.orcidKumar, S. [0000-0001-7126-9814]
dc.identifier.urihttp://hdl.handle.net/2440/9554
dc.language.isoen
dc.publisherAmer Soc Biochemistry Molecular Biology Inc
dc.rights© 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
dc.source.urihttps://doi.org/10.1074/jbc.m011273200
dc.subjectMandible
dc.subjectCytosol
dc.subjectAnimals
dc.subjectMice
dc.subjectSodium
dc.subjectAmiloride
dc.subjectGlutathione Transferase
dc.subjectPeptides
dc.subjectSodium Channels
dc.subjectRecombinant Fusion Proteins
dc.subjectDNA, Complementary
dc.subjectVirulence Factors, Bordetella
dc.subjectPatch-Clamp Techniques
dc.subjectAmino Acid Sequence
dc.subjectAmino Acid Motifs
dc.subjectProtein Structure, Tertiary
dc.subjectSequence Homology, Amino Acid
dc.subjectPhosphorylation
dc.subjectDose-Response Relationship, Drug
dc.subjectPlasmids
dc.subjectMolecular Sequence Data
dc.subjectEpithelial Sodium Channels
dc.titleRoles of the C termini of α-, β-, and γ-subunits of epithelial Na⁺ channels (ENaC) in regulating ENaC and mediating its inhibition by cytosolic Na⁺
dc.title.alternativeRoles of the C termini of alpha-, beta-, and gamma-subunits of epithelial Na(+) channels (ENaC) in regulating ENaC and mediating its inhibition by cytosolic Na(+)
dc.typeJournal article
pubs.publication-statusPublished

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