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Type: Journal article
Title: The Activity of the Epithelial Sodium Channels Is Regulated by Caveolin-1 via a Nedd4-2-dependent Mechanism
Author: Lee, I.
Campbell, C.
Song, S.
Day, M.
Kumar, S.
Cook, D.
Dinudom, A.
Citation: Journal of Biological Chemistry, 2009; 284(19):12663-12669
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2009
ISSN: 0021-9258
Statement of
Il-Ha Lee, Craig R. Campbell, Sung-Hee Song, Margot L. Day, Sharad Kumar, David I. Cook and Anuwat Dinudom
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.
Keywords: Kidney Tubules, Collecting
Thyroid Gland
Cells, Cultured
Cell Membrane
Rats, Inbred F344
Ubiquitin-Protein Ligases
Caveolin 1
Endosomal Sorting Complexes Required for Transport
Epithelial Sodium Channels
Epithelial Sodium Channel Blockers
Nedd4 Ubiquitin Protein Ligases
Rights: Copyright © 2009 by American Society for Biochemistry and Molecular Biolog
DOI: 10.1074/jbc.M809737200
Grant ID:
Appears in Collections:Aurora harvest 5
Medicine publications

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