Nedd4-2-dependent ubiquitylation and regulation of the cardiac potassium channel hERG1.
Détails
ID Serval
serval:BIB_01A640BC771F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Nedd4-2-dependent ubiquitylation and regulation of the cardiac potassium channel hERG1.
Périodique
Journal of Molecular and Cellular Cardiology
ISSN
1095-8584 (Electronic)
ISSN-L
0022-2828
Statut éditorial
Publié
Date de publication
2011
Volume
51
Numéro
1
Pages
90-98
Langue
anglais
Résumé
The voltage-gated cardiac potassium channel hERG1 (human ether-à-gogo-related gene 1) plays a key role in the repolarization phase of the cardiac action potential (AP). Mutations in its gene, KCNH2, can lead to defects in the biosynthesis and maturation of the channel, resulting in congenital long QT syndrome (LQTS). To identify the molecular mechanisms regulating the density of hERG1 channels at the plasma membrane, we investigated channel ubiquitylation by ubiquitin ligase Nedd4-2, a post-translational regulatory mechanism previously linked to other ion channels. We found that whole-cell hERG1 currents recorded in HEK293 cells were decreased upon neural precursor cell expressed developmentally down-regulated 4-2 (Nedd4-2) co-expression. The amount of hERG1 channels in total HEK293 lysates and at the cell surface, as assessed by Western blot and biotinylation assays, respectively, were concomitantly decreased. Nedd4-2 and hERG1 interact via a PY motif located in the C-terminus of hERG1. Finally, we determined that Nedd4-2 mediates ubiquitylation of hERG1 and that deletion of this motif affects Nedd4-2-dependent regulation. These results suggest that ubiquitylation of the hERG1 protein by Nedd4-2, and its subsequent down-regulation, could represent an important mechanism for modulation of the duration of the human cardiac action potential.
Pubmed
Web of science
Création de la notice
29/06/2011 13:35
Dernière modification de la notice
20/08/2019 13:23