Deubiquitylating enzyme USP2 counteracts Nedd4-2-mediated downregulation of KCNQ1 potassium channels.

Détails

ID Serval
serval:BIB_C888498BAA1B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Deubiquitylating enzyme USP2 counteracts Nedd4-2-mediated downregulation of KCNQ1 potassium channels.
Périodique
Heart Rhythm
Auteur⸱e⸱s
Krzystanek K., Rasmussen H.B., Grunnet M., Staub O., Olesen S.P., Abriel H., Jespersen T.
ISSN
1556-3871 (Electronic)
ISSN-L
1547-5271
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
9
Numéro
3
Pages
440-448
Langue
anglais
Résumé
BACKGROUND: KCNQ1 (Kv7.1), together with its KCNE β subunits, plays a pivotal role both in the repolarization of cardiac tissue and in water and salt transport across epithelial membranes. Nedd4/Nedd4-like (neuronal precursor cell-expressed developmentally downregulated 4) ubiquitin-protein ligases interact with the KCNQ1 potassium channel through a PY motif located in the C terminus of KCNQ1. This interaction induces ubiquitylation of KCNQ1, resulting in a reduced surface density of the channel. It was reported recently that the epithelial sodium channel is regulated by the reverse process-deubiquitylation-mediated by USP2 (ubiquitin-specific protease 2).
OBJECTIVE: In this article, we investigated whether deubiquitylation may regulate KCNQ1 channel complexes.
METHODS: In this study, we used electrophysiology, biochemistry, and confocal microscopy.
RESULTS: Electrophysiological investigations of KCNQ1/KCNE1 proteins coexpressed with USP2-45 or USP2-69 isoforms and Nedd4-2 in Xenopus laevis oocytes and mammalian cells revealed that both USP2 isoforms counter the Nedd4-2-specific downregulation of I(Ks). Biochemical studies showed that the total and surface-expressed KCNQ1 protein was more abundant when coexpressed with USP2 and Nedd4-2 as compared with Nedd4-2 alone. Western blotting revealed partial protection against covalent attachment of ubiquitin moieties on KCNQ1 when USP2 was coexpressed with Nedd4-2. Coimmunoprecipitation assays suggested that USP2 can bind to KCNQ1 independently of the PY motif. Immunocytochemistry confirmed that USP2 restores the membrane localization of KCNQ1.
CONCLUSION: These results demonstrate that USP2 can be a potent regulator of KCNQ1 surface density. USP2, which is well expressed in many tissues, may therefore be important in controlling the KCNQ1 channel dynamics in vivo.
Mots-clé
I-Ks, Kv7.1, minK, Potassium channels, Ubiquitylation, Deubiquitylation, Membrane protein regulation
Pubmed
Web of science
Création de la notice
02/11/2011 10:03
Dernière modification de la notice
20/10/2020 10:12
Données d'usage