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https://hdl.handle.net/2440/58689
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dc.contributor.author | Lee, I. | - |
dc.contributor.author | Campbell, C. | - |
dc.contributor.author | Song, S. | - |
dc.contributor.author | Day, M. | - |
dc.contributor.author | Kumar, S. | - |
dc.contributor.author | Cook, D. | - |
dc.contributor.author | Dinudom, A. | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | Journal of Biological Chemistry, 2009; 284(19):12663-12669 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.issn | 1083-351X | - |
dc.identifier.uri | http://hdl.handle.net/2440/58689 | - |
dc.description.abstract | It has recently been shown that the epithelial Na+ channel (ENaC) is compartmentalized in caveolin-rich lipid rafts and that pharmacological depletion of membrane cholesterol, which disrupts lipid raft formation, decreases the activity of ENaC. Here we show, for the first time, that a signature protein of caveolae, caveolin-1 (Cav-1), down-regulates the activity and membrane surface expression of ENaC. Physical interaction between ENaC and Cav-1 was also confirmed in a coimmunoprecipitation assay. We found that the effect of Cav-1 on ENaC requires the activity of Nedd4-2, a ubiquitin protein ligase of the Nedd4 family, which is known to induce ubiquitination and internalization of ENaC. The effect of Cav-1 on ENaC requires the proline-rich motifs at the C termini of the β- and γ-subunits of ENaC, the binding motifs that mediate interaction with Nedd4-2. Taken together, our data suggest that Cav-1 inhibits the activity of ENaC by decreasing expression of ENaC at the cell membrane via a mechanism that involves the promotion of Nedd4-2-dependent internalization of the channel. | - |
dc.description.statementofresponsibility | Il-Ha Lee, Craig R. Campbell, Sung-Hee Song, Margot L. Day, Sharad Kumar, David I. Cook and Anuwat Dinudom | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Biochemistry Molecular Biology Inc | - |
dc.rights | Copyright © 2009 by American Society for Biochemistry and Molecular Biolog | - |
dc.source.uri | http://dx.doi.org/10.1074/jbc.m809737200 | - |
dc.subject | Kidney Tubules, Collecting | - |
dc.subject | Thyroid Gland | - |
dc.subject | Cells, Cultured | - |
dc.subject | Cell Membrane | - |
dc.subject | Animals | - |
dc.subject | Rats, Inbred F344 | - |
dc.subject | Mice | - |
dc.subject | Rats | - |
dc.subject | Ubiquitin-Protein Ligases | - |
dc.subject | Immunoblotting | - |
dc.subject | Immunoprecipitation | - |
dc.subject | Down-Regulation | - |
dc.subject | Caveolin 1 | - |
dc.subject | Endosomal Sorting Complexes Required for Transport | - |
dc.subject | Epithelial Sodium Channels | - |
dc.subject | Epithelial Sodium Channel Blockers | - |
dc.subject | Nedd4 Ubiquitin Protein Ligases | - |
dc.title | The Activity of the Epithelial Sodium Channels Is Regulated by Caveolin-1 via a Nedd4-2-dependent Mechanism | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1074/jbc.M809737200 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/DP0774320 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/DP0774320 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Kumar, S. [0000-0001-7126-9814] | - |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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