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MTOC translocation modulates IS formation and controls sustained T cell signaling
The translocation of the microtubule-organizing center (MTOC) toward the nascent immune synapse (IS) is an early step in lymphocyte activation initiated by T cell receptor (TCR) signaling. The molecular mechanisms that control the physical movement of the lymphocyte MTOC remain largely unknown. We h...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528574/ https://www.ncbi.nlm.nih.gov/pubmed/18779373 http://dx.doi.org/10.1083/jcb.200801014 |
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author | Martín-Cófreces, Noa B. Robles-Valero, Javier Cabrero, J. Román Mittelbrunn, María Gordón-Alonso, Mónica Sung, Ching-Hwa Alarcón, Balbino Vázquez, Jesús Sánchez-Madrid, Francisco |
author_facet | Martín-Cófreces, Noa B. Robles-Valero, Javier Cabrero, J. Román Mittelbrunn, María Gordón-Alonso, Mónica Sung, Ching-Hwa Alarcón, Balbino Vázquez, Jesús Sánchez-Madrid, Francisco |
author_sort | Martín-Cófreces, Noa B. |
collection | PubMed |
description | The translocation of the microtubule-organizing center (MTOC) toward the nascent immune synapse (IS) is an early step in lymphocyte activation initiated by T cell receptor (TCR) signaling. The molecular mechanisms that control the physical movement of the lymphocyte MTOC remain largely unknown. We have studied the role of the dynein–dynactin complex, a microtubule-based molecular motor, in the process of T cell activation during T cell antigen–presenting cell cognate immune interactions. Impairment of dynein–dynactin complex activity, either by overexpressing the p50-dynamitin component of dynactin to disrupt the complex or by knocking down dynein heavy chain expression to prevent its formation, inhibited MTOC translocation after TCR antigen priming. This resulted in a strong reduction in the phosphorylation of molecules such as ζ chain–associated protein kinase 70 (ZAP70), linker of activated T cells (LAT), and Vav1; prevented the supply of molecules to the IS from intracellular pools, resulting in a disorganized and dysfunctional IS architecture; and impaired interleukin-2 production. Together, these data reveal MTOC translocation as an important mechanism underlying IS formation and sustained T cell signaling. |
format | Text |
id | pubmed-2528574 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-25285742009-03-08 MTOC translocation modulates IS formation and controls sustained T cell signaling Martín-Cófreces, Noa B. Robles-Valero, Javier Cabrero, J. Román Mittelbrunn, María Gordón-Alonso, Mónica Sung, Ching-Hwa Alarcón, Balbino Vázquez, Jesús Sánchez-Madrid, Francisco J Cell Biol Research Articles The translocation of the microtubule-organizing center (MTOC) toward the nascent immune synapse (IS) is an early step in lymphocyte activation initiated by T cell receptor (TCR) signaling. The molecular mechanisms that control the physical movement of the lymphocyte MTOC remain largely unknown. We have studied the role of the dynein–dynactin complex, a microtubule-based molecular motor, in the process of T cell activation during T cell antigen–presenting cell cognate immune interactions. Impairment of dynein–dynactin complex activity, either by overexpressing the p50-dynamitin component of dynactin to disrupt the complex or by knocking down dynein heavy chain expression to prevent its formation, inhibited MTOC translocation after TCR antigen priming. This resulted in a strong reduction in the phosphorylation of molecules such as ζ chain–associated protein kinase 70 (ZAP70), linker of activated T cells (LAT), and Vav1; prevented the supply of molecules to the IS from intracellular pools, resulting in a disorganized and dysfunctional IS architecture; and impaired interleukin-2 production. Together, these data reveal MTOC translocation as an important mechanism underlying IS formation and sustained T cell signaling. The Rockefeller University Press 2008-09-08 /pmc/articles/PMC2528574/ /pubmed/18779373 http://dx.doi.org/10.1083/jcb.200801014 Text en © 2008 Martín-Cófreces et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Martín-Cófreces, Noa B. Robles-Valero, Javier Cabrero, J. Román Mittelbrunn, María Gordón-Alonso, Mónica Sung, Ching-Hwa Alarcón, Balbino Vázquez, Jesús Sánchez-Madrid, Francisco MTOC translocation modulates IS formation and controls sustained T cell signaling |
title | MTOC translocation modulates IS formation and controls sustained T cell signaling |
title_full | MTOC translocation modulates IS formation and controls sustained T cell signaling |
title_fullStr | MTOC translocation modulates IS formation and controls sustained T cell signaling |
title_full_unstemmed | MTOC translocation modulates IS formation and controls sustained T cell signaling |
title_short | MTOC translocation modulates IS formation and controls sustained T cell signaling |
title_sort | mtoc translocation modulates is formation and controls sustained t cell signaling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528574/ https://www.ncbi.nlm.nih.gov/pubmed/18779373 http://dx.doi.org/10.1083/jcb.200801014 |
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