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dc.contributor.authorPark, Sung-Soo
dc.contributor.authorPonce-Balbuena, Daniela
dc.contributor.authorKuick, Rork
dc.contributor.authorGuerrero-Serna, Guadalupe
dc.contributor.authorYoon, Justin
dc.contributor.authorMellacheruvu, Dattatreya
dc.contributor.authorConlon, Kevin P
dc.contributor.authorBasrur, Venkatesha
dc.contributor.authorNesvizhskii, Alexey I
dc.contributor.authorJalife, Jose 
dc.contributor.authorRual, Jean-François
dc.date.accessioned2021-06-22T09:40:03Z
dc.date.available2021-06-22T09:40:03Z
dc.date.issued2020-09
dc.identifier.citationMol Cell Proteomics. 2020; 19(9):1436-1449es_ES
dc.identifier.issn1535-9476es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13174
dc.description.abstractKir2.1, a strong inward rectifier potassium channel encoded by the KCNJ2 gene, is a key regulator of the resting membrane potential of the cardiomyocyte and plays an important role in controlling ventricular excitation and action potential duration in the human heart. Mutations in KCNJ2 result in inheritable cardiac diseases in humans, e.g. the type-1 Andersen-Tawil syndrome (ATS1). Understanding the molecular mechanisms that govern the regulation of inward rectifier potassium currents by Kir2.1 in both normal and disease contexts should help uncover novel targets for therapeutic intervention in ATS1 and other Kir2.1-associated channelopathies. The information available to date on protein-protein interactions involving Kir2.1 channels remains limited. Additional efforts are necessary to provide a comprehensive map of the Kir2.1 interactome. Here we describe the generation of a comprehensive map of the Kir2.1 interactome using the proximity-labeling approach BioID. Most of the 218 high-confidence Kir2.1 channel interactions we identified are novel and encompass various molecular mechanisms of Kir2.1 function, ranging from intracellular trafficking to cross-talk with the insulin-like growth factor receptor signaling pathway, as well as lysosomal degradation. Our map also explores the variations in the interactome profiles of Kir2.1WT versus Kir2.1Δ314-315, a trafficking deficient ATS1 mutant, thus uncovering molecular mechanisms whose malfunctions may underlie ATS1 disease. Finally, using patch-clamp analysis, we validate the functional relevance of PKP4, one of our top BioID interactors, to the modulation of Kir2.1-controlled inward rectifier potassium currents. Our results validate the power of our BioID approach in identifying functionally relevant Kir2.1 interactors and underline the value of our Kir2.1 interactome as a repository for numerous novel biological hypotheses on Kir2.1 and Kir2.1-associated diseases.es_ES
dc.description.sponsorshipThis work was supported by the National Institutes of Health (NIH) through the National Heart, Lung, and Blood Institute (NHLBI) grant R01HL122352 awarded to J.J., as well as the National Institute of General Medical Sciences (NIGMS) grant R01GM094231 and the National Cancer Institute (NCI) grant U24CA210967 awarded to A.I.N. R.K. is supported by the NCI support grant P30CA046592 awarded to the University of Michigan Rogel Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleKir2.1 Interactome Mapping Uncovers PKP4 as a Modulator of the Kir2.1-Regulated Inward Rectifier Potassium Currentses_ES
dc.typeArtículoes_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.format.volume19es_ES
dc.format.number9es_ES
dc.format.page1436-1449es_ES
dc.identifier.doi10.1074/mcp.RA120.002071es_ES
dc.contributor.funderNational Institutes of Health (United States)es_ES
dc.contributor.funderNational Heart, Lung, and Blood Institute (United States)es_ES
dc.contributor.funderNational Institute of General Medical Sciences (United States)es_ES
dc.contributor.funderNational Cancer Institute (United States)es_ES
dc.contributor.funderUniversity of Michigan Rogel Cancer Center (United States)es_ES
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1074/mcp.RA120.002071es_ES
dc.identifier.journalMolecular & Cellular Proteomicses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Arritmias Cardíacases_ES
dc.repisalud.institucionCNICes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This item is licensed under a: Attribution-NonCommercial-NoDerivatives 4.0 Internacional