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dc.contributor.authorGonzalez-Granado, Jose Maria 
dc.contributor.authorSilvestre-Roig, Carlos 
dc.contributor.authorRocha-Perugini, Vera 
dc.contributor.authorTrigueros-Motos, Laia 
dc.contributor.authorCibrian, Danay 
dc.contributor.authorMorlino, Giulia 
dc.contributor.authorBlanco-Berrocal, Marta 
dc.contributor.authorOsorio, Fernando Garcia
dc.contributor.authorFreije, José María Pérez
dc.contributor.authorLópez-Otín, Carlos
dc.contributor.authorSanchez-Madrid, Francisco 
dc.contributor.authorAndres, Vicente 
dc.date.accessioned2019-07-17T07:32:02Z
dc.date.available2019-07-17T07:32:02Z
dc.date.issued2014-04-22
dc.identifier.citationSci Signal. 2014; 7(322):ra37es_ES
dc.identifier.issn1945-0877es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7919
dc.description.abstractIn many cell types, nuclear A-type lamins regulate multiple cellular functions, including higher-order genome organization, DNA replication and repair, gene transcription, and signal transduction; however, their role in specialized immune cells remains largely unexplored. We showed that the abundance of A-type lamins was almost negligible in resting naïve T lymphocytes, but was increased upon activation of the T cell receptor (TCR). The increase in lamin-A was an early event that accelerated formation of the immunological synapse between T cells and antigen-presenting cells. Polymerization of F-actin in T cells is a critical step for immunological synapse formation, and lamin-A interacted with the linker of nucleoskeleton and cytoskeleton (LINC) complex to promote F-actin polymerization. We also showed that lamin-A expression accelerated TCR clustering and led to enhanced downstream signaling, including extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, as well as increased target gene expression. Pharmacological inhibition of the ERK pathway reduced lamin-A-dependent T cell activation. Moreover, mice lacking lamin-A in immune cells exhibited impaired T cell responses in vivo. These findings underscore the importance of A-type lamins for TCR activation and identify lamin-A as a previously unappreciated regulator of the immune response.es_ES
dc.description.sponsorshipSpanish Ministerio de Economia y Competitividad (MINECO) [SAF2011-25834, SAF2010-16044]; Comunidad de Madrid [INDISNET-S2011/BMD-2332]; Instituto de Salud Carlos III (ISCIII) [RD12/0042/0028, RD12/0042/0056, CP11/00145]; Progeria Research Foundation [PRF 2012-42]; European Commission [ERC-2011AdG 294340-GENTRIS, 317916-Liphos]; Sara Borrell ISCIII program [CP11/00145]; Miguel Servet ISCIII program [CP11/00145]; Fundacion Mario Losantos del Campo; Fundacion Ferrer para la Investigacion; Obra Social Cajastur; Spanish MINECO; Pro-CNIC Foundationes_ES
dc.language.isoenges_ES
dc.publisherAAASes_ES
dc.relation.isversionofPostprintes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshActin Cytoskeleton es_ES
dc.subject.meshActins es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshHumans es_ES
dc.subject.meshImmunological Synapses es_ES
dc.subject.meshJurkat Cells es_ES
dc.subject.meshLamin Type A es_ES
dc.subject.meshLymphocyte Activation es_ES
dc.subject.meshMAP Kinase Signaling System es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshMitogen-Activated Protein Kinase 1 es_ES
dc.subject.meshMitogen-Activated Protein Kinase 3 es_ES
dc.subject.meshReceptors, Antigen, T-Celles_ES
dc.subject.meshT-Lymphocytes es_ES
dc.titleNuclear envelope lamin-A couples actin dynamics with immunological synapse architecture and T cell activationes_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID24757177es_ES
dc.format.volume7es_ES
dc.format.number322es_ES
dc.format.pagera37es_ES
dc.identifier.doi10.1126/scisignal.2004872es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderProgeria Research Foundationes_ES
dc.contributor.funderEuropean Commissiones_ES
dc.contributor.funderFundación Ferreres_ES
dc.contributor.funderFundación Cajastures_ES
dc.contributor.funderFundación ProCNICes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1937-9145es_ES
dc.identifier.journalScience signalinges_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genéticaes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Comunicación Intercelular en la Respuesta Inflamatoriaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/294340/EUes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/317916/EUes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2011-25834es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2010-16044es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0042/0028es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0042/0056es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CP11/00145es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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