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oai:repisalud.isciii.es:20.500.12105/79192024-09-27T08:21:55Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Gonzalez-Granado, Jose Maria author Silvestre-Roig, Carlos author Rocha-Perugini, Vera author Trigueros-Motos, Laia author Cibrian, Danay author Morlino, Giulia author Blanco-Berrocal, Marta author Osorio, Fernando Garcia author Freije, José María Pérez author López-Otín, Carlos author Sanchez-Madrid, Francisco author Andres, Vicente author 2014-04-22 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. Sci Signal. 2014; 7(322):ra37 10.1126/scisignal.2004872 1937-9145 1945-0877 Science signaling 24757177 http://hdl.handle.net/20.500.12105/7919 Nuclear envelope lamin-A couples actin dynamics with immunological synapse architecture and T cell activation