| Autor: |
Álvaro Gómez-Morón, Sergio Alegre-Gómez, Rocio Ramirez-Muñoz, Alicia Hernaiz-Esteban, Carlos Carrasco-Padilla, Camila Scagnetti, Óscar Aguilar-Sopeña, Marta García-Gil, Aldo Borroto, Raul Torres-Ruiz, Sandra Rodriguez-Perales, Francisco Sánchez-Madrid, Noa Beatriz Martín-Cófreces, Pedro Roda-Navarro |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Communications Biology, Vol 7, Iss 1, Pp 1-17 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2399-3642 |
| DOI: |
10.1038/s42003-024-06605-8 |
| Popis: |
Abstract 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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