The activity of the epithelial sodium channels is regulated by caveolin-1 via a Nedd4-2-dependent mechanism
| Autor: | Sharad Kumar, Sung-Hee Song, Craig Campbell, David I. Cook, Anuwat Dinudom, Margot L. Day, Il-Ha Lee |
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| Přispěvatelé: | Lee, Il-Ha, Campbell, Craig R, Song, Sung-Hee, Day, Margot L, Kumar, Sharad, Cook, David I, Dinudom, Anuwat |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Epithelial sodium channel
inorganic chemicals Nedd4 Ubiquitin Protein Ligases Ubiquitin-Protein Ligases media_common.quotation_subject Caveolin 1 Immunoblotting Thyroid Gland Down-Regulation NEDD4 ubiquitination Biochemistry Cell membrane Mice caveolin 1 Caveolae Epithelial Sodium Channel Blockers medicine Animals Immunoprecipitation Kidney Tubules Collecting ubiquitin protein ligase NEDD4 Epithelial Sodium Channels Internalization Molecular Biology Lipid raft Cells Cultured media_common Endosomal Sorting Complexes Required for Transport biology Chemistry urogenital system Cell Membrane Cell Biology respiratory system Rats Inbred F344 Rats Ubiquitin ligase Cell biology Membrane Transport Structure Function and Biogenesis medicine.anatomical_structure biology.protein cardiovascular system hormones hormone substitutes and hormone antagonists |
| Popis: | 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 beta- and gamma-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. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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