| First Author | Santos LC | Year | 2016 |
| Journal | Immunol Cell Biol | Volume | 94 |
| Issue | 10 | Pages | 981-993 |
| PubMed ID | 27359298 | Mgi Jnum | J:322366 |
| Mgi Id | MGI:6838590 | Doi | 10.1038/icb.2016.61 |
| Citation | Santos LC, et al. (2016) Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability. Immunol Cell Biol 94(10):981-993 |
| abstractText | The immunological synapse formed between a T-cell and an antigen-presenting cell is important for cell-cell communication during T-cell-mediated immune responses. Immunological synapse formation begins with stimulation of the T-cell receptor (TCR). TCR microclusters are assembled and transported to the center of the immunological synapse in an actin polymerization-dependent process. However, the physical link between TCR and actin remains elusive. Here we show that lymphocyte-specific Crk-associated substrate (Cas-L), a member of a force sensing protein family, is required for transport of TCR microclusters and for establishing synapse stability. We found that Cas-L is phosphorylated at TCR microclusters in an actin polymerization-dependent fashion. Furthermore, Cas-L participates in a positive feedback loop leading to amplification of Ca(2+) signaling, inside-out integrin activation, and actomyosin contraction. We propose a new role for Cas-L in T-cell activation as a mechanical transducer linking TCR microclusters to the underlying actin network and coordinating multiple actin-dependent structures in the immunological synapse. Our studies highlight the importance of mechanotransduction processes in T-cell-mediated immune responses. |
