Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability

Luís C. Santos, David A. Blair, Sudha Kumari, Michael Cammer, Thomas Iskratsch, Olivier Herbin, Konstantina Alexandropoulos, Michael L. Dustin, Michael Sheetz

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)981-993
Number of pages13
JournalImmunology and Cell Biology
Volume94
Issue number10
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Santos, L. C., Blair, D. A., Kumari, S., Cammer, M., Iskratsch, T., Herbin, O., Alexandropoulos, K., Dustin, M. L., & Sheetz, M. (2016). Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability. Immunology and Cell Biology, 94(10), 981-993. https://doi.org/10.1038/icb.2016.61