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

12 Citations (Scopus)

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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Immunological Synapses
T-Cell Antigen Receptor
Polymerization
Actins
T-Lymphocytes
Crk-Associated Substrate Protein
Actomyosin
Viral Tumor Antigens
Antigen-Presenting Cells
Transducers
Integrins
Cell Communication
Synapses
Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability. / Santos, Luís C.; Blair, David A.; Kumari, Sudha; Cammer, Michael; Iskratsch, Thomas; Herbin, Olivier; Alexandropoulos, Konstantina; Dustin, Michael L.; Sheetz, Michael.

In: Immunology and Cell Biology, Vol. 94, No. 10, 01.11.2016, p. 981-993.

Research output: Contribution to journalArticle

Santos, LC, Blair, DA, Kumari, S, Cammer, M, Iskratsch, T, Herbin, O, Alexandropoulos, K, Dustin, ML & Sheetz, M 2016, 'Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability', Immunology and Cell Biology, vol. 94, no. 10, pp. 981-993. https://doi.org/10.1038/icb.2016.61
Santos, Luís C. ; Blair, David A. ; Kumari, Sudha ; Cammer, Michael ; Iskratsch, Thomas ; Herbin, Olivier ; Alexandropoulos, Konstantina ; Dustin, Michael L. ; Sheetz, Michael. / Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability. In: Immunology and Cell Biology. 2016 ; Vol. 94, No. 10. pp. 981-993.
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