KCNE4 suppresses Kv1.3 currents by modulating trafficking, surface expression and channel gating

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• dc.contributor.author Solé, Lauraca
• dc.contributor.author Roura Ferrer, Meritxellca
• dc.contributor.author Pérez Verdaguer, Mireiaca
• dc.contributor.author Oliveras, Annaca
• dc.contributor.author Calvo, Mariaca
• dc.contributor.author Fernández-Fernández, José Manuel, 1967-ca
• dc.contributor.author Felipe, Antonioca
• dc.date.accessioned 2016-01-21T15:14:55Z
• dc.date.available 2016-01-21T15:14:55Z
• dc.date.issued 2009
• dc.description.abstract Voltage-dependent potassium channels (Kv) play a crucial role in the activation and proliferation of leukocytes. Kv channels are either homo- or hetero-oligomers. This composition modulates their surface expression and serves as a mechanism for regulating channel activity. Kv channel interaction with accessory subunits provides mechanisms for channels to respond to stimuli beyond changes in membrane potential. Here, we demonstrate that KCNE4 (potassium voltage-gated channel subfamily E member 4), but not KCNE2, functions as an inhibitory Kv1.3 partner in leukocytes. Kv1.3 trafficking, targeting and activity are altered by the presence of KCNE4. KCNE4 decreases current density, slows activation, accelerates inactivation, increases cumulative inactivation, retains Kv1.3 in the ER and impairs channel targeting to lipid raft microdomains. KCNE4 associates with Kv1.3 in the ER and decreases the number of Kv1.3 channels at the cell surface, which diminishes cell excitability. Kv1.3 and KCNE4 are differentially regulated upon activation or immunosuppression in macrophages. Thus, lipopolysaccharide-induced activation increases Kv1.3 and KCNE4 mRNA, whereas dexamethasone triggers a decrease in Kv1.3 with no changes in KCNE4. The channelosome composition determines the activity and affects surface expression and membrane localization. Therefore, KCNE4 association might play a crucial role in controlling immunological responses. Our results indicate that KCNE ancillary subunits could be new targets for immunomodulation.ca
• dc.description.sponsorship This study was supported by the Ministerio de Ciencia e Innovación (MICINN), Spain (BFU2005-00695, BFU2008-00431 and CSD2008-00005 to A.F. and SAF2006-13893-C02-02 to J.M.F.-F.). L.S. holds fellowships from the MICINN and ‘Fundación La Caixa’. The FI program of the Generalitat de Catalunya supported M.R.-F. and M.P.-V.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Solé L, Roura-Ferrer M, Pérez-Verdaguer M, Oliveras A, Calvo M, Fernández-Fernández JM et al. KCNE4 suppresses Kv1.3 currents by modulating trafficking, surface expression and channel gating. Journal of cell science. 2009;122(Pt 20):3738-48. DOI: 10.1242/jcs.056689ca
• dc.identifier.doi http://dx.doi.org/10.1242/jcs.056689
• dc.identifier.issn 0021-9533
• dc.identifier.uri http://hdl.handle.net/10230/25627
• dc.language.iso engca
• dc.publisher Company of Biologistsca
• dc.relation.ispartof Journal of cell science. 2009;122(Pt 20):3738-48
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/BFU2005-00695
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2006-13893
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2008-00431
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2008-00005
• dc.rights © Company of Biologists http://jcs.biologists.org/content/joces/122/20/3738.full.pdf DOI 10.1242/jcs.056689ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.keyword KCNE regulatory subunits
• dc.subject.keyword Kv1.3
• dc.subject.keyword Leukocytes
• dc.subject.keyword Trafficking
• dc.subject.keyword Channelosome
• dc.subject.keyword Surface expression
• dc.subject.other Canals de potassica
• dc.subject.other Proteïnesca
• dc.subject.other RNA missatgerca
• dc.title KCNE4 suppresses Kv1.3 currents by modulating trafficking, surface expression and channel gatingca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca