dc.contributor.author | Gonzalez-Granado, Jose Maria | |
dc.contributor.author | Silvestre-Roig, Carlos | |
dc.contributor.author | Rocha-Perugini, Vera | |
dc.contributor.author | Trigueros-Motos, Laia | |
dc.contributor.author | Cibrian, Danay | |
dc.contributor.author | Morlino, Giulia | |
dc.contributor.author | Blanco-Berrocal, Marta | |
dc.contributor.author | Osorio, Fernando Garcia | |
dc.contributor.author | Freije, José María Pérez | |
dc.contributor.author | López-Otín, Carlos | |
dc.contributor.author | Sanchez-Madrid, Francisco | |
dc.contributor.author | Andres, Vicente | |
dc.date.accessioned | 2019-07-17T07:32:02Z | |
dc.date.available | 2019-07-17T07:32:02Z | |
dc.date.issued | 2014-04-22 | |
dc.identifier.citation | Sci Signal. 2014; 7(322):ra37 | es_ES |
dc.identifier.issn | 1945-0877 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7919 | |
dc.description.abstract | In 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.sponsorship | Spanish 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 Foundation | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Association for the Advancement of Science (AAAS) | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Actin Cytoskeleton | es_ES |
dc.subject.mesh | Actins | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Immunological Synapses | es_ES |
dc.subject.mesh | Jurkat Cells | es_ES |
dc.subject.mesh | Lamin Type A | es_ES |
dc.subject.mesh | Lymphocyte Activation | es_ES |
dc.subject.mesh | MAP Kinase Signaling System | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Knockout | es_ES |
dc.subject.mesh | Mitogen-Activated Protein Kinase 1 | es_ES |
dc.subject.mesh | Mitogen-Activated Protein Kinase 3 | es_ES |
dc.subject.mesh | Receptors, Antigen, T-Cell | es_ES |
dc.subject.mesh | T-Lymphocytes | es_ES |
dc.title | Nuclear envelope lamin-A couples actin dynamics with immunological synapse architecture and T cell activation | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 24757177 | es_ES |
dc.format.volume | 7 | es_ES |
dc.format.number | 322 | es_ES |
dc.format.page | ra37 | es_ES |
dc.identifier.doi | 10.1126/scisignal.2004872 | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Progeria Research Foundation | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Fundación Ferrer Investigación | |
dc.contributor.funder | Fundación Cajastur | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1937-9145 | es_ES |
dc.identifier.journal | Science signaling | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genética | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Comunicación Intercelular en la Respuesta Inflamatoria | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/294340/EU | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/317916/EU | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2011-25834 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2010-16044 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12/0042/0028 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12/0042/0056 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/CP11/00145 | es_ES |
dc.rights.accessRights | open access | es_ES |