Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7919
Nuclear envelope lamin-A couples actin dynamics with immunological synapse architecture and T cell activation
Gonzalez-Granado, Jose Maria CNIC | Silvestre-Roig, Carlos CNIC | Rocha-Perugini, Vera CNIC | Trigueros-Motos, Laia CNIC | Cibrian, Danay CNIC | Morlino, Giulia CNIC | Blanco-Berrocal, Marta CNIC | Osorio, Fernando Garcia | Freije, José María Pérez | López-Otín, Carlos | Sanchez-Madrid, Francisco CNIC | Andres, Vicente CNIC
Sci Signal. 2014; 7(322):ra37
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.
Actin Cytoskeleton | Actins | Animals | Humans | Immunological Synapses | Jurkat Cells | Lamin Type A | Lymphocyte Activation | MAP Kinase Signaling System | Mice | Mice, Knockout | Mitogen-Activated Protein Kinase 1 | Mitogen-Activated Protein Kinase 3 | Receptors, Antigen, T-Cell | T-Lymphocytes