Human T-cell receptor triggering requires inactivation of Lim kinase-1 by Slingshot-1 phosphatase.

Actin 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 th...

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Detalles Bibliográficos
Autores: Gómez-Morón, Álvaro, Alegre Gómez, Sergio, Ramírez Muñoz, Rocío, Hernaiz-Esteban, Alicia, Carrasco-Padilla, Carlos, Scagnetti, Camila, Aguilar-Sopeña, Óscar, García-Gil, Marta, Borroto, Aldo, Torres-Ruiz, Raul, Rodríguez Perales, Sandra, Sánchez-Madrid, Francisco, Martín-Cófreces, Noa Beatriz, Roda Navarro, Pedro
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/120021
Acceso en línea:https://hdl.handle.net/20.500.14352/120021
Access Level:acceso abierto
Palabra clave:616.079
T cell
immunological synapse
cytoskeleton dynamics
Ciencias Biomédicas
Inmunología
24 Ciencias de la Vida
32 Ciencias Médicas
2412 Inmunología
Descripción
Sumario:Actin 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.

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