http://purl.uniprot.org/citations/22024150 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/22024150 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/22024150 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundKCNQ1 (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).ObjectiveIn this article, we investigated whether deubiquitylation may regulate KCNQ1 channel complexes.MethodsIn this study, we used electrophysiology, biochemistry, and confocal microscopy.ResultsElectrophysiological 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.ConclusionThese 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."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.hrthm.2011.10.026"xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.hrthm.2011.10.026"xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Staub O."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Staub O."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Abriel H."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Abriel H."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Grunnet M."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Grunnet M."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Olesen S.P."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Olesen S.P."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Rasmussen H.B."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Rasmussen H.B."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Jespersen T."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Jespersen T."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Krzystanek K."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/author | "Krzystanek K."xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/name | "Heart Rhythm"xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/name | "Heart Rhythm"xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/pages | "440-448"xsd:string |
http://purl.uniprot.org/citations/22024150 | http://purl.uniprot.org/core/pages | "440-448"xsd:string |