Gómez-Morón, ÁlvaroAlegre Gómez, SergioRamírez Muñoz, RocíoHernaiz-Esteban, AliciaCarrasco-Padilla, CarlosScagnetti, CamilaAguilar-Sopeña, ÓscarGarcía-Gil, MartaBorroto, AldoTorres-Ruiz, RaulRodríguez Perales, SandraSánchez-Madrid, FranciscoMartín-Cófreces, Noa BeatrizRoda Navarro, Pedro2025-05-132025-05-132024-07-30Human T-cell receptor triggering requires inactivation of Lim kinase-1 by Slingshot-1 phosphatase. Gómez-Morón Á, Alegre-Gómez S, Ramirez-Muñoz R, Hernaiz-Esteban A, Carrasco-Padilla C, Scagnetti C, Aguilar-Sopeña Ó, García-Gil M, Borroto A, Torres-Ruiz R, Rodriguez-Perales S, Sánchez-Madrid F, Martín-Cófreces NB, Roda-Navarro P. Commun Biol. 2024 Jul 30;7(1):918.10.1038/S42003-024-06605-8https://hdl.handle.net/20.500.14352/120021Actin dynamics control early T-cell receptor (TCR) signalling during T-cell activation. However, the precise regulation of initial actin rearrangements is not completely understood. Here, we have investigated the regulatory role of the phosphatase Slingshot-1 (SSH1) in this process. Our data show that SSH1 rapidly polarises to nascent cognate synaptic contacts and later relocalises to peripheral F-actin networks organised at the mature immunological synapse. Knockdown of SSH1 expression by CRISPR/Cas9-mediated genome editing or small interfering RNA reveal a regulatory role for SSH1 in CD3ε conformational change, allowing Nck binding and proper downstream signalling and immunological synapse organisation. TCR triggering induces SSH1-mediated activation of actin dynamics through a mechanism mediated by Limk-1 inactivation. These data suggest that during early TCR activation, SSH1 is required for rapid F-actin rearrangements that mediate initial conformational changes of the TCR, integrin organisation and proximal signalling events for proper synapse organisation. Therefore, the SSH1 and Limk-1 axis is a key regulatory element for full T cell activation.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.1038/s42003-024-06605-839080357open access616.079T cellimmunological synapsecytoskeleton dynamicsCiencias BiomédicasInmunología24 Ciencias de la Vida32 Ciencias Médicas2412 Inmunología