LFA-1 and kindlin-3 enable the collaborative transport of SLP-76 microclusters by myosin and dynein motors
| Autor: | Stephen C. Bunnell, Keith P. Eidell, Alenka Lovy, Ken Nguyen, Frank A Scangarello, Michael J. Ophir, Maria-Cristina Seminario, Hayley I. Muendlein, Nicholas R. Sylvain |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | J Cell Sci |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Integrin engagement within the immune synapse enhances T cell activation, but our understanding of this process is incomplete. In response to T cell receptor (TCR) ligation, SLP-76 (LCP2), ADAP (FYB1) and SKAP55 (SKAP1) are recruited into microclusters and activate integrins via the effectors talin-1 and kindlin-3 (FERMT3). We postulated that integrins influence the centripetal transport and signaling of SLP-76 microclusters via these linkages. We show that contractile myosin filaments surround and are co-transported with SLP-76 microclusters, and that TCR ligand density governs the centripetal movement of both structures. Centripetal transport requires formin activity, actomyosin contraction, microtubule integrity and dynein motor function. Although immobilized VLA-4 (α4β1 integrin) and LFA-1 (αLβ2 integrin) ligands arrest the centripetal movement of SLP-76 microclusters and myosin filaments, VLA-4 acts distally, while LFA-1 acts in the lamellum. Integrin β2, kindlin-3 and zyxin are required for complete centripetal transport, while integrin β1 and talin-1 are not. CD69 upregulation is similarly dependent on integrin β2, kindlin-3 and zyxin, but not talin-1. These findings highlight the integration of cytoskeletal systems within the immune synapse and reveal extracellular ligand-independent roles for LFA-1 and kindlin-3.This article has an associated First Person interview with the first author of the paper. |
| Databáze: | OpenAIRE |
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