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In vivo quantitative analysis of Talin turnover in response to force
Cell adhesion to the extracellular matrix (ECM) allows cells to form and maintain three-dimensional tissue architecture. Cell–ECM adhesions are stabilized upon exposure to mechanical force. In this study, we used quantitative imaging and mathematical modeling to gain mechanistic insight into how int...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710244/ https://www.ncbi.nlm.nih.gov/pubmed/26446844 http://dx.doi.org/10.1091/mbc.E15-05-0304 |
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author | Hákonardóttir, Guðlaug Katrín López-Ceballos, Pablo Herrera-Reyes, Alejandra Donají Das, Raibatak Coombs, Daniel Tanentzapf, Guy |
author_facet | Hákonardóttir, Guðlaug Katrín López-Ceballos, Pablo Herrera-Reyes, Alejandra Donají Das, Raibatak Coombs, Daniel Tanentzapf, Guy |
author_sort | Hákonardóttir, Guðlaug Katrín |
collection | PubMed |
description | Cell adhesion to the extracellular matrix (ECM) allows cells to form and maintain three-dimensional tissue architecture. Cell–ECM adhesions are stabilized upon exposure to mechanical force. In this study, we used quantitative imaging and mathematical modeling to gain mechanistic insight into how integrin-based adhesions respond to increased and decreased mechanical forces. A critical means of regulating integrin-based adhesion is provided by modulating the turnover of integrin and its adhesion complex (integrin adhesion complex [IAC]). The turnover of the IAC component Talin, a known mechanosensor, was analyzed using fluorescence recovery after photobleaching. Experiments were carried out in live, intact flies in genetic backgrounds that increased or decreased the force applied on sites of adhesion. This analysis showed that when force is elevated, the rate of assembly of new adhesions increases such that cell–ECM adhesion is stabilized. Moreover, under conditions of decreased force, the overall rate of turnover, but not the proportion of adhesion complex components undergoing turnover, increases. Using point mutations, we identify the key functional domains of Talin that mediate its response to force. Finally, by fitting a mathematical model to the data, we uncover the mechanisms that mediate the stabilization of ECM-based adhesion during development. |
format | Online Article Text |
id | pubmed-4710244 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-47102442016-01-20 In vivo quantitative analysis of Talin turnover in response to force Hákonardóttir, Guðlaug Katrín López-Ceballos, Pablo Herrera-Reyes, Alejandra Donají Das, Raibatak Coombs, Daniel Tanentzapf, Guy Mol Biol Cell Articles Cell adhesion to the extracellular matrix (ECM) allows cells to form and maintain three-dimensional tissue architecture. Cell–ECM adhesions are stabilized upon exposure to mechanical force. In this study, we used quantitative imaging and mathematical modeling to gain mechanistic insight into how integrin-based adhesions respond to increased and decreased mechanical forces. A critical means of regulating integrin-based adhesion is provided by modulating the turnover of integrin and its adhesion complex (integrin adhesion complex [IAC]). The turnover of the IAC component Talin, a known mechanosensor, was analyzed using fluorescence recovery after photobleaching. Experiments were carried out in live, intact flies in genetic backgrounds that increased or decreased the force applied on sites of adhesion. This analysis showed that when force is elevated, the rate of assembly of new adhesions increases such that cell–ECM adhesion is stabilized. Moreover, under conditions of decreased force, the overall rate of turnover, but not the proportion of adhesion complex components undergoing turnover, increases. Using point mutations, we identify the key functional domains of Talin that mediate its response to force. Finally, by fitting a mathematical model to the data, we uncover the mechanisms that mediate the stabilization of ECM-based adhesion during development. The American Society for Cell Biology 2015-11-05 /pmc/articles/PMC4710244/ /pubmed/26446844 http://dx.doi.org/10.1091/mbc.E15-05-0304 Text en © 2015 Hákonardóttir, López-Ceballos, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Hákonardóttir, Guðlaug Katrín López-Ceballos, Pablo Herrera-Reyes, Alejandra Donají Das, Raibatak Coombs, Daniel Tanentzapf, Guy In vivo quantitative analysis of Talin turnover in response to force |
title | In vivo quantitative analysis of Talin turnover in response to force |
title_full | In vivo quantitative analysis of Talin turnover in response to force |
title_fullStr | In vivo quantitative analysis of Talin turnover in response to force |
title_full_unstemmed | In vivo quantitative analysis of Talin turnover in response to force |
title_short | In vivo quantitative analysis of Talin turnover in response to force |
title_sort | in vivo quantitative analysis of talin turnover in response to force |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710244/ https://www.ncbi.nlm.nih.gov/pubmed/26446844 http://dx.doi.org/10.1091/mbc.E15-05-0304 |
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