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dc.contributor.author | Garcia-Ortiz, Almudena | |
dc.contributor.author | Martin-Cofreces, Noa B. | |
dc.contributor.author | Ibiza, Sales | |
dc.contributor.author | Ortega, Angel | |
dc.contributor.author | Izquierdo-Alvarez, Alicia | |
dc.contributor.author | Trullo, Antonio | |
dc.contributor.author | Victor, Victor Manuel | |
dc.contributor.author | Calvo, Enrique | |
dc.contributor.author | Sot, Begona | |
dc.contributor.author | Martinez-Ruiz, Antonio | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Sanchez-Madrid, Francisco | |
dc.contributor.author | Serrador, Juan M. | |
dc.date.accessioned | 2017-10-20T10:23:13Z | |
dc.date.available | 2017-10-20T10:23:13Z | |
dc.date.issued | 2017 | |
dc.identifier | ISI:000400423600004 | |
dc.identifier.citation | PLoS Biol. 2017; 15(4):e2000653 | |
dc.identifier.issn | 1545-7885 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5124 | |
dc.description.abstract | The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-theta (PKC-theta) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of beta-actin and PKC-theta from the lamellipodium-like distal (d)-SMAC, promoting PKC-theta. activation. Furthermore, eNOS-derived NO S-nitrosylated beta-actin on Cys374 and impaired actin binding to profilin-1 (PFN1), as confirmed with the transnitrosylating agent S-nitroso-L-cysteine (Cys-NO). The importance of NO and the formation of PFN1-actin complexes on the regulation of PKC-theta. was corroborated by overexpression of PFN1- and actin-binding defective mutants of beta-actin (C374S) and PFN1 (H119E), respectively, which reduced the coalescence of PKC-theta. at the c-SMAC. These findings unveil a novel NO-dependent mechanism by which the actin cytoskeleton controls the organization and activation of signaling microclusters at the IS. | |
dc.description.sponsorship | Institute de Salud Carlos III (ISCIII, Spanish Government) (grant number PI10/02136) to J.M.S. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ERC (grant number ERC-2011-AdG294340-GENTRIS) to F.S.M. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MINECO/FEDER (grant number SAF2015-69396-R) to J.M.S. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MINECO (grant number B102015-67580-P) to J.V. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Institute de Salud Carlos III (ISCIII, Spanish Government) (grant number PI16/1083) to V.M.V. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Institute de Salud Carlos III (ISCIII, Spanish Government) (grant number PI15/00107, and I3SNS program) to A.M.R. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Institute de Salud Carlos III (ISCIII, Spanish Government) (grant number IPT13-0001 SGEFI/FEDER) to J.V. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Fundacion Domingo Martinez http://www.fundaciondm.org (Ayuda a la Investigacion 2015 Area de Biomedicina y Salud) to J.M.S. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | |
dc.language.iso | eng | |
dc.publisher | Public Library of Science (PLOS) | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | NITRIC-OXIDE SYNTHASE | |
dc.subject | T-CELL-ACTIVATION | |
dc.subject | IMMUNOLOGICAL SYNAPSE | |
dc.subject | RETROGRADE FLOW | |
dc.subject | ARP2/3 COMPLEX | |
dc.subject | PROTEIN | |
dc.subject | RECEPTOR | |
dc.subject | POLYMERIZATION | |
dc.subject | POLARIZATION | |
dc.subject | CYTOSKELETON | |
dc.title | eNOS S-nitrosylates beta-actin on Cys374 and regulates PKC-theta at the immune synapse by impairing actin binding to profilin-1 | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 28394935 | |
dc.format.volume | 15 | |
dc.identifier.doi | 10.1371/journal.pbio.2000653 | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.1371/journal.pbio.2000653 | |
dc.identifier.journal | Plos Biology | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Comunicación Intercelular en la Respuesta Inflamatoria | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Proteómica cardiovascular | |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Proteómica / Metabolómica | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/294340/EU | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2015-69396-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI10/02136 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BIO2015-67580-P | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI16/108 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI15/00107 | es_ES |
dc.rights.accessRights | open access | es_ES |