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dc.contributor.authorGarcia-Ortiz, Almudena
dc.contributor.authorMartin-Cofreces, Noa B. 
dc.contributor.authorIbiza, Sales
dc.contributor.authorOrtega, Angel
dc.contributor.authorIzquierdo-Alvarez, Alicia
dc.contributor.authorTrullo, Antonio
dc.contributor.authorVictor, Victor Manuel
dc.contributor.authorCalvo, Enrique 
dc.contributor.authorSot, Begona
dc.contributor.authorMartinez-Ruiz, Antonio
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorSanchez-Madrid, Francisco 
dc.contributor.authorSerrador, Juan M.
dc.date.accessioned2017-10-20T10:23:13Z
dc.date.available2017-10-20T10:23:13Z
dc.date.issued2017
dc.identifierISI:000400423600004
dc.identifier.citationPLoS Biol. 2017; 15(4):e2000653
dc.identifier.issn1545-7885
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5124
dc.description.abstractThe 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.sponsorshipInstitute 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.isoeng
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectNITRIC-OXIDE SYNTHASE
dc.subjectT-CELL-ACTIVATION
dc.subjectIMMUNOLOGICAL SYNAPSE
dc.subjectRETROGRADE FLOW
dc.subjectARP2/3 COMPLEX
dc.subjectPROTEIN
dc.subjectRECEPTOR
dc.subjectPOLYMERIZATION
dc.subjectPOLARIZATION
dc.subjectCYTOSKELETON
dc.titleeNOS S-nitrosylates beta-actin on Cys374 and regulates PKC-theta at the immune synapse by impairing actin binding to profilin-1
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID28394935
dc.format.volume15
dc.identifier.doi10.1371/journal.pbio.2000653
dc.contributor.funderInstituto de Salud Carlos III - ISCIII
dc.contributor.funderEuropean Research Council
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)
dc.contributor.funderEC-European Commission
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pbio.2000653
dc.identifier.journalPlos Biology
dc.repisalud.orgCNICCNIC::Grupos de investigación::Comunicación Intercelular en la Respuesta Inflamatoria
dc.repisalud.orgCNICCNIC::Grupos de investigación::Proteómica cardiovascular
dc.repisalud.orgCNICCNIC::Unidades técnicas::Proteómica / Metabolómica
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/294340/EUes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-69396-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI10/02136es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BIO2015-67580-Pes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16/108es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI15/00107es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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