Gonzalez-Granado, Jose MariaSilvestre-Roig, CarlosRocha-Perugini, VeraTrigueros-Motos, LaiaCibrian, DanayMorlino, GiuliaBlanco-Berrocal, MartaOsorio, Fernando GarciaFreije, José María PérezLópez-Otín, CarlosSanchez-Madrid, FranciscoAndres, Vicente2019-07-172019-07-172014-04-22Sci Signal. 2014; 7(322):ra371945-0877http://hdl.handle.net/20.500.12105/7919In 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.engAMhttp://creativecommons.org/licenses/by-nc-sa/4.0/Actin CytoskeletonActinsAnimalsHumansImmunological SynapsesJurkat CellsLamin Type ALymphocyte ActivationMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Receptors, Antigen, T-CellT-LymphocytesAtribución-NoComercial-CompartirIgual 4.0 Internacional247571777322ra3710.1126/scisignal.20048721937-9145Science signalingopen access