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Coordinated integrin activation by actin-dependent force during T-cell migration

For a cell to move forward it must convert chemical energy into mechanical propulsion. Force produced by actin polymerization can generate traction across the plasma membrane by transmission through integrins to their ligands. However, the role this force plays in integrin activation is unknown. Her...

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Detalles Bibliográficos
Autores principales: Nordenfelt, Pontus, Elliott, Hunter L., Springer, Timothy A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062559/
https://www.ncbi.nlm.nih.gov/pubmed/27721490
http://dx.doi.org/10.1038/ncomms13119
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author Nordenfelt, Pontus
Elliott, Hunter L.
Springer, Timothy A.
author_facet Nordenfelt, Pontus
Elliott, Hunter L.
Springer, Timothy A.
author_sort Nordenfelt, Pontus
collection PubMed
description For a cell to move forward it must convert chemical energy into mechanical propulsion. Force produced by actin polymerization can generate traction across the plasma membrane by transmission through integrins to their ligands. However, the role this force plays in integrin activation is unknown. Here we show that integrin activity and cytoskeletal dynamics are reciprocally linked, where actin-dependent force itself appears to regulate integrin activity. We generated fluorescent tension-sensing constructs of integrin αLβ2 (LFA-1) to visualize intramolecular tension during cell migration. Using quantitative imaging of migrating T cells, we correlate tension in the αL or β2 subunit with cell and actin dynamics. We find that actin engagement produces tension within the β2 subunit to induce and stabilize an active integrin conformational state and that this requires intact talin and kindlin motifs. This supports a general mechanism where localized actin polymerization can coordinate activation of the complex machinery required for cell migration.
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spelling pubmed-50625592016-10-27 Coordinated integrin activation by actin-dependent force during T-cell migration Nordenfelt, Pontus Elliott, Hunter L. Springer, Timothy A. Nat Commun Article For a cell to move forward it must convert chemical energy into mechanical propulsion. Force produced by actin polymerization can generate traction across the plasma membrane by transmission through integrins to their ligands. However, the role this force plays in integrin activation is unknown. Here we show that integrin activity and cytoskeletal dynamics are reciprocally linked, where actin-dependent force itself appears to regulate integrin activity. We generated fluorescent tension-sensing constructs of integrin αLβ2 (LFA-1) to visualize intramolecular tension during cell migration. Using quantitative imaging of migrating T cells, we correlate tension in the αL or β2 subunit with cell and actin dynamics. We find that actin engagement produces tension within the β2 subunit to induce and stabilize an active integrin conformational state and that this requires intact talin and kindlin motifs. This supports a general mechanism where localized actin polymerization can coordinate activation of the complex machinery required for cell migration. Nature Publishing Group 2016-10-10 /pmc/articles/PMC5062559/ /pubmed/27721490 http://dx.doi.org/10.1038/ncomms13119 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Nordenfelt, Pontus
Elliott, Hunter L.
Springer, Timothy A.
Coordinated integrin activation by actin-dependent force during T-cell migration
title Coordinated integrin activation by actin-dependent force during T-cell migration
title_full Coordinated integrin activation by actin-dependent force during T-cell migration
title_fullStr Coordinated integrin activation by actin-dependent force during T-cell migration
title_full_unstemmed Coordinated integrin activation by actin-dependent force during T-cell migration
title_short Coordinated integrin activation by actin-dependent force during T-cell migration
title_sort coordinated integrin activation by actin-dependent force during t-cell migration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062559/
https://www.ncbi.nlm.nih.gov/pubmed/27721490
http://dx.doi.org/10.1038/ncomms13119
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