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INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells
T cell antigen receptor–proximal signaling components, Rho-family GTPases, and formin proteins DIA1 and FMNL1 have been implicated in centrosome reorientation to the immunological synapse of T lymphocytes. However, the role of these molecules in the reorientation process is not yet defined. Here we...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444772/ https://www.ncbi.nlm.nih.gov/pubmed/22986496 http://dx.doi.org/10.1083/jcb.201202137 |
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author | Andrés-Delgado, Laura Antón, Olga M. Bartolini, Francesca Ruiz-Sáenz, Ana Correas, Isabel Gundersen, Gregg G. Alonso, Miguel A. |
author_facet | Andrés-Delgado, Laura Antón, Olga M. Bartolini, Francesca Ruiz-Sáenz, Ana Correas, Isabel Gundersen, Gregg G. Alonso, Miguel A. |
author_sort | Andrés-Delgado, Laura |
collection | PubMed |
description | T cell antigen receptor–proximal signaling components, Rho-family GTPases, and formin proteins DIA1 and FMNL1 have been implicated in centrosome reorientation to the immunological synapse of T lymphocytes. However, the role of these molecules in the reorientation process is not yet defined. Here we find that a subset of microtubules became rapidly stabilized and that their α-tubulin subunit posttranslationally detyrosinated after engagement of the T cell receptor. Formation of stabilized, detyrosinated microtubules required the formin INF2, which was also found to be essential for centrosome reorientation, but it occurred independently of T cell receptor–induced massive tyrosine phosphorylation. The FH2 domain, which was mapped as the INF2 region involved in centrosome repositioning, was able to mediate the formation of stable, detyrosinated microtubules and to restore centrosome translocation in DIA1-, FMNL1-, Rac1-, and Cdc42-deficient cells. Further experiments indicated that microtubule stabilization was required for centrosome polarization. Our work identifies INF2 and stable, detyrosinated microtubules as central players in centrosome reorientation in T cells. |
format | Online Article Text |
id | pubmed-3444772 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34447722013-03-17 INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells Andrés-Delgado, Laura Antón, Olga M. Bartolini, Francesca Ruiz-Sáenz, Ana Correas, Isabel Gundersen, Gregg G. Alonso, Miguel A. J Cell Biol Research Articles T cell antigen receptor–proximal signaling components, Rho-family GTPases, and formin proteins DIA1 and FMNL1 have been implicated in centrosome reorientation to the immunological synapse of T lymphocytes. However, the role of these molecules in the reorientation process is not yet defined. Here we find that a subset of microtubules became rapidly stabilized and that their α-tubulin subunit posttranslationally detyrosinated after engagement of the T cell receptor. Formation of stabilized, detyrosinated microtubules required the formin INF2, which was also found to be essential for centrosome reorientation, but it occurred independently of T cell receptor–induced massive tyrosine phosphorylation. The FH2 domain, which was mapped as the INF2 region involved in centrosome repositioning, was able to mediate the formation of stable, detyrosinated microtubules and to restore centrosome translocation in DIA1-, FMNL1-, Rac1-, and Cdc42-deficient cells. Further experiments indicated that microtubule stabilization was required for centrosome polarization. Our work identifies INF2 and stable, detyrosinated microtubules as central players in centrosome reorientation in T cells. The Rockefeller University Press 2012-09-17 /pmc/articles/PMC3444772/ /pubmed/22986496 http://dx.doi.org/10.1083/jcb.201202137 Text en © 2012 Andrés-Delgado 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.rupress.org/terms). 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 Andrés-Delgado, Laura Antón, Olga M. Bartolini, Francesca Ruiz-Sáenz, Ana Correas, Isabel Gundersen, Gregg G. Alonso, Miguel A. INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells |
title | INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells |
title_full | INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells |
title_fullStr | INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells |
title_full_unstemmed | INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells |
title_short | INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells |
title_sort | inf2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in t cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444772/ https://www.ncbi.nlm.nih.gov/pubmed/22986496 http://dx.doi.org/10.1083/jcb.201202137 |
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