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http://hdl.handle.net/2445/120567
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DC Field | Value | Language |
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dc.contributor.author | Martínez Mármol, Ramón | - |
dc.contributor.author | Styrczewska, Katarzyna | - |
dc.contributor.author | Pérez Verdaguer, Mireia | - |
dc.contributor.author | Vallejo Gracia, Albert | - |
dc.contributor.author | Comes i Beltrán, Núria | - |
dc.contributor.author | Sorkin, Alexander | - |
dc.contributor.author | Felipe Campo, Antonio | - |
dc.date.accessioned | 2018-03-08T15:02:14Z | - |
dc.date.available | 2018-03-08T15:02:14Z | - |
dc.date.issued | 2017-02-10 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | http://hdl.handle.net/2445/120567 | - |
dc.description.abstract | The voltage-dependent potassium channel Kv1.3 plays essential physiological functions in the immune system. Kv1.3, regulating the membrane potential, facilitates downstream Ca2+ -dependent pathways and becomes concentrated in specific membrane microdomains that serve as signaling platforms. Increased and/or delocalized expression of the channel is observed at the onset of several autoimmune diseases. In this work, we show that adenosine (ADO), which is a potent endogenous modulator, stimulates PKC, thereby causing immunosuppression. PKC activation triggers down-regulation of Kv1.3 by inducing a clathrin-mediated endocytic event that targets the channel to lysosomal-degradative compartments. Therefore, the abundance of Kv1.3 at the cell surface decreases, which is clearly compatible with an effective anti-inflammatory response. This mechanism requires ubiquitination of Kv1.3, catalyzed by the E3 ubiquitin-ligase Nedd4-2. Postsynaptic density protein 95 (PSD-95), a member of the MAGUK family, recruits Kv1.3 into lipid-raft microdomains and protects the channel against ubiquitination and endocytosis. Therefore, the Kv1.3/PSD-95 association fine-tunes the anti-inflammatory response in leukocytes. Because Kv1.3 is a promising multi-therapeutic target against human pathologies, our results have physiological relevance. In addition, this work elucidates the ADO-dependent PKC-mediated molecular mechanism that triggers immunomodulation by targeting Kv1.3 in leukocytes. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1038/srep42395 | - |
dc.relation.ispartof | Scientific Reports, 2017, vol. 7, num. 42395 | - |
dc.relation.uri | https://doi.org/10.1038/srep42395 | - |
dc.rights | cc-by (c) Martínez Mármol, Ramón et al., 2017 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Sistema nerviós | - |
dc.subject.classification | Ubiqüitina | - |
dc.subject.other | Nervous system | - |
dc.subject.other | Ubiquitin | - |
dc.title | Ubiquitination mediates Kv1.3 endocytosis as a mechanism for protein Kinase C-dependent modulation | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 670571 | - |
dc.date.updated | 2018-03-08T15:02:14Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 28186199 | - |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Biomedicina) |
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