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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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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. |
format | Online Article Text |
id | pubmed-5121033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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