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

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...

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Autores principales: Santos, Luís C, Blair, David A, Kumari, Sudha, Cammer, Michael, Iskratsch, Thomas, Herbin, Olivier, Alexandropoulos, Konstantina, Dustin, Michael L, Sheetz, Michael P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121033/
https://www.ncbi.nlm.nih.gov/pubmed/27359298
http://dx.doi.org/10.1038/icb.2016.61
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author Santos, Luís C
Blair, David A
Kumari, Sudha
Cammer, Michael
Iskratsch, Thomas
Herbin, Olivier
Alexandropoulos, Konstantina
Dustin, Michael L
Sheetz, Michael P
author_facet Santos, Luís C
Blair, David A
Kumari, Sudha
Cammer, Michael
Iskratsch, Thomas
Herbin, Olivier
Alexandropoulos, Konstantina
Dustin, Michael L
Sheetz, Michael P
author_sort Santos, Luís C
collection PubMed
description 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.
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spelling pubmed-51210332016-12-15 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 P Immunol Cell Biol Original Articles 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. Nature Publishing Group 2016-11-01 2016 /pmc/articles/PMC5121033/ /pubmed/27359298 http://dx.doi.org/10.1038/icb.2016.61 Text en © 2016 Australasian Society for Immunology Inc. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/3.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Santos, Luís C
Blair, David A
Kumari, Sudha
Cammer, Michael
Iskratsch, Thomas
Herbin, Olivier
Alexandropoulos, Konstantina
Dustin, Michael L
Sheetz, Michael P
Actin polymerization‐dependent activation of Cas‐L promotes immunological synapse stability
title Actin polymerization‐dependent activation of Cas‐L promotes immunological synapse stability
title_full Actin polymerization‐dependent activation of Cas‐L promotes immunological synapse stability
title_fullStr Actin polymerization‐dependent activation of Cas‐L promotes immunological synapse stability
title_full_unstemmed Actin polymerization‐dependent activation of Cas‐L promotes immunological synapse stability
title_short Actin polymerization‐dependent activation of Cas‐L promotes immunological synapse stability
title_sort actin polymerization‐dependent activation of cas‐l promotes immunological synapse stability
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121033/
https://www.ncbi.nlm.nih.gov/pubmed/27359298
http://dx.doi.org/10.1038/icb.2016.61
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