Regulation of the cardiac voltage-gated Na+ channel (H1) by the ubiquitin-protein ligase Nedd4.

Détails

ID Serval
serval:BIB_E32017C59816
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Regulation of the cardiac voltage-gated Na+ channel (H1) by the ubiquitin-protein ligase Nedd4.
Périodique
FEBS letters
Auteur(s)
Abriel H., Kamynina E., Horisberger J.D., Staub O.
ISSN
0014-5793
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
466
Numéro
2-3
Pages
377-380
Langue
anglais
Résumé
The cardiac voltage-gated Na+ channel H1, involved in the generation of cardiac action potential, contains a C-terminal PY motif (xPPxY). Since PY motifs are known ligands to WW domains, we investigated their role for H1 regulation and the possible involvement of the WW domain containing ubiquitin-protein ligase Nedd4, taking advantage of the Xenopus oocyte system. Mutation of the PY motif leads to higher peak currents when compared to wild-type channel. Moreover, co-expression of Nedd4 reduced the peak currents, whereas an enzymatically inactive Nedd4 mutant increased them, likely by competing with endogenous Nedd4. The effect of Nedd4 was not observed in the PY motif mutated channel or in the skeletal muscle voltage-gated Na+ channel, which lacks a PY motif. We conclude that H1 may be regulated by Nedd4 depending on WW-PY interaction, and on an active ubiquitination site.
Mots-clé
Amino Acid Motifs, Amino Acid Sequence, Animals, Calcium-Binding Proteins, Gene Expression Regulation, Ion Channel Gating, Ligases, Molecular Sequence Data, Mutagenesis, Site-Directed, Myocardium, Rats, Sequence Homology, Amino Acid, Sodium Channels, Ubiquitin-Protein Ligases, Xenopus
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 11:56
Dernière modification de la notice
20/08/2019 17:06
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