RT Journal Article
T1 Human T-cell receptor triggering requires inactivation of Lim kinase-1 by Slingshot-1 phosphatase.
A1 Gómez-Morón, Álvaro
A1 Alegre Gómez, Sergio
A1 Ramírez Muñoz, Rocío
A1 Hernaiz-Esteban, Alicia
A1 Carrasco-Padilla, Carlos
A1 Scagnetti, Camila
A1 Aguilar-Sopeña, Óscar
A1 García-Gil, Marta
A1 Borroto, Aldo
A1 Torres-Ruiz, Raul
A1 Rodríguez Perales, Sandra
A1 Sánchez-Madrid, Francisco
A1 Martín-Cófreces, Noa Beatriz
A1 Roda Navarro, Pedro
AB 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.
PB Nature Research
YR 2024
FD 2024-07-30
LK https://hdl.handle.net/20.500.14352/120021
UL https://hdl.handle.net/20.500.14352/120021
LA eng
NO Human 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.
NO Agencia Estatal de Investigación
DS Docta Complutense
RD 20 abr 2026