Deubiquitylation regulates activation and proteolytic cleavage of ENaC

Détails

ID Serval
serval:BIB_8BE56FEB6132
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Deubiquitylation regulates activation and proteolytic cleavage of ENaC
Périodique
Journal of the American Society of Nephrology
Auteur(s)
Ruffieux-Daidie D., Poirot O., Boulkroun S., Verrey F., Kellenberger S., Staub O.
ISSN
1533-3450
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
19
Numéro
11
Pages
2170-2180
Langue
anglais
Résumé
The epithelial sodium channel (ENaC) is critical for sodium and BP homeostasis. ENaC is regulated by Nedd4-2-mediated ubiquitylation, which leads to its internalization; this process can be reversed by deubiquitylation, which is regulated by the aldosterone-induced enzyme Usp2-45. In a second regulatory pathway, ENaC can be activated by luminal serine protease-mediated cleavage of its extracellular loops. Whether these two regulatory processes interact, however, is unknown. Here, in HEK293 cells stably transfected with ENaC, Usp2-45 interacted with ENaC, leading to deubiquitylation of the channel and stimulation of ENaC activity >20-fold. This was accompanied by a modest increase in cell surface expression of ENaC and by proteolytic cleavage of alphaENaC and gammaENaC at their extracellular loops. When endocytosis was inhibited with dominant negative dynamin (DynK44R), channel density and gammaENaC cleavage were increased, but alphaENaC cleavage and ENaC activity were not augmented. When Usp2-45 was coexpressed with DynK44R, both alphaENaC cleavage and activity were recovered. In summary, these data suggest that Usp2-45 deubiquitylation of ENaC enhances the proteolytic activation of both alphaENaC and gammaENaC, possibly by inducing a conformational change and by interfering with endocytosis, respectively
Mots-clé
Amiloride , Animals , Cell Line , Cell Membrane , chemistry , Endocytosis , Endopeptidases , Epithelial Sodium Channel , genetics , Homeostasis , Humans , metabolism , Peptide Hydrolases , pharmacology , Protein Subunits , Rats , Recombinant Proteins , Sodium Channel Blockers , Switzerland , Transfection , Ubiquitin-Protein Ligases , Ubiquitination
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/01/2009 23:14
Dernière modification de la notice
08/05/2019 21:44
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