A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel

Détails

ID Serval
serval:BIB_A12AA8C5870B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel
Périodique
FASEB Journal
Auteur(s)
Kamynina  E., Debonneville  C., Bens  M., Vandewalle  A., Staub  O.
ISSN
0892-6638 (Print)
Statut éditorial
Publié
Date de publication
01/2001
Volume
15
Numéro
1
Pages
204-214
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Résumé
Liddle's syndrome is a form of inherited hypertension linked to mutations in the genes encoding the epithelial Na+ channel (ENaC). These mutations alter or delete PY motifs involved in protein-protein interactions with a ubiquitin-protein ligase, Nedd4. Here we show that Na+ transporting cells, derived from mouse cortical collecting duct, express two Nedd4 proteins with different structural organization and characteristics of ENaC regulation: 1) the classical Nedd4 (herein referred to as Nedd4-1) containing one amino-terminal C2, three WW, and one HECT-ubiquitin protein ligase domain and 2) a novel Nedd4 protein (Nedd4-2), homologous to Xenopus Nedd4 and comprising four WW, one HECT, yet lacking a C2 domain. Nedd4-2, but not Nedd4-1, inhibits ENaC activity when coexpressed in Xenopus oocytes and this property correlates with the ability to bind to ENaC, as only Nedd4-2 coimmunoprecipitates with ENaC. Furthermore, this interaction depends on the presence of at least one PY motif in the ENaC complex and on WW domains 3 and 4 in Nedd4-2. Thus, these results suggest that the novel suppressor protein Nedd4-2 is the regulator of ENaC and hence a potential susceptibility gene for arterial hypertension.
Mots-clé
Amino Acid Motifs Amino Acid Sequence Animals Binding Sites Calcium-Binding Proteins/chemistry/genetics/*metabolism Cloning, Molecular Ligases/chemistry/genetics/*metabolism Mice Molecular Sequence Data Mutation Oocytes/drug effects/metabolism Protein Binding Protein Isoforms/chemistry/genetics/metabolism Protein Structure, Tertiary RNA, Messenger/analysis/genetics Rats Sequence Alignment *Sodium Channel Blockers Sodium Channels/metabolism *Ubiquitin-Protein Ligases Xenopus laevis
Pubmed
Web of science
Création de la notice
24/01/2008 13:03
Dernière modification de la notice
20/08/2019 15:07
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