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CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics

Focal adhesions are cellular structures through which both mechanical forces and regulatory signals are transmitted. Two focal adhesion-associated proteins, Crk-associated substrate (CAS) and vinculin, were both independently shown to be crucial for the ability of cells to transmit mechanical forces...

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Autores principales: Janoštiak, Radoslav, Brábek, Jan, Auernheimer, Vera, Tatárová, Zuzana, Lautscham, Lena A., Dey, Tuli, Gemperle, Jakub, Merkel, Rudolf, Goldmann, Wolfgang H., Fabry, Ben, Rösel, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Basel 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901934/
https://www.ncbi.nlm.nih.gov/pubmed/23974298
http://dx.doi.org/10.1007/s00018-013-1450-x
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author Janoštiak, Radoslav
Brábek, Jan
Auernheimer, Vera
Tatárová, Zuzana
Lautscham, Lena A.
Dey, Tuli
Gemperle, Jakub
Merkel, Rudolf
Goldmann, Wolfgang H.
Fabry, Ben
Rösel, Daniel
author_facet Janoštiak, Radoslav
Brábek, Jan
Auernheimer, Vera
Tatárová, Zuzana
Lautscham, Lena A.
Dey, Tuli
Gemperle, Jakub
Merkel, Rudolf
Goldmann, Wolfgang H.
Fabry, Ben
Rösel, Daniel
author_sort Janoštiak, Radoslav
collection PubMed
description Focal adhesions are cellular structures through which both mechanical forces and regulatory signals are transmitted. Two focal adhesion-associated proteins, Crk-associated substrate (CAS) and vinculin, were both independently shown to be crucial for the ability of cells to transmit mechanical forces and to regulate cytoskeletal tension. Here, we identify a novel, direct binding interaction between CAS and vinculin. This interaction is mediated by the CAS SRC homology 3 domain and a proline-rich sequence in the hinge region of vinculin. We show that CAS localization in focal adhesions is partially dependent on vinculin, and that CAS–vinculin coupling is required for stretch-induced activation of CAS at the Y410 phosphorylation site. Moreover, CAS–vinculin binding significantly affects the dynamics of CAS and vinculin within focal adhesions as well as the size of focal adhesions. Finally, disruption of CAS binding to vinculin reduces cell stiffness and traction force generation. Taken together, these findings strongly implicate a crucial role of CAS–vinculin interaction in mechanosensing and focal adhesion dynamics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-013-1450-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-39019342014-01-30 CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics Janoštiak, Radoslav Brábek, Jan Auernheimer, Vera Tatárová, Zuzana Lautscham, Lena A. Dey, Tuli Gemperle, Jakub Merkel, Rudolf Goldmann, Wolfgang H. Fabry, Ben Rösel, Daniel Cell Mol Life Sci Research Article Focal adhesions are cellular structures through which both mechanical forces and regulatory signals are transmitted. Two focal adhesion-associated proteins, Crk-associated substrate (CAS) and vinculin, were both independently shown to be crucial for the ability of cells to transmit mechanical forces and to regulate cytoskeletal tension. Here, we identify a novel, direct binding interaction between CAS and vinculin. This interaction is mediated by the CAS SRC homology 3 domain and a proline-rich sequence in the hinge region of vinculin. We show that CAS localization in focal adhesions is partially dependent on vinculin, and that CAS–vinculin coupling is required for stretch-induced activation of CAS at the Y410 phosphorylation site. Moreover, CAS–vinculin binding significantly affects the dynamics of CAS and vinculin within focal adhesions as well as the size of focal adhesions. Finally, disruption of CAS binding to vinculin reduces cell stiffness and traction force generation. Taken together, these findings strongly implicate a crucial role of CAS–vinculin interaction in mechanosensing and focal adhesion dynamics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-013-1450-x) contains supplementary material, which is available to authorized users. Springer Basel 2013-08-25 2014 /pmc/articles/PMC3901934/ /pubmed/23974298 http://dx.doi.org/10.1007/s00018-013-1450-x Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Research Article
Janoštiak, Radoslav
Brábek, Jan
Auernheimer, Vera
Tatárová, Zuzana
Lautscham, Lena A.
Dey, Tuli
Gemperle, Jakub
Merkel, Rudolf
Goldmann, Wolfgang H.
Fabry, Ben
Rösel, Daniel
CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics
title CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics
title_full CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics
title_fullStr CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics
title_full_unstemmed CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics
title_short CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics
title_sort cas directly interacts with vinculin to control mechanosensing and focal adhesion dynamics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901934/
https://www.ncbi.nlm.nih.gov/pubmed/23974298
http://dx.doi.org/10.1007/s00018-013-1450-x
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