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The role of focal adhesion anchoring domains of CAS in mechanotransduction

CAS is a docking protein, which was shown to act as a mechanosensor in focal adhesions. The unique assembly of structural domains in CAS is important for its function as a mechanosensor. The tension within focal adhesions is transmitted to a stretchable substrate domain of CAS by focal adhesion-targ...

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Autores principales: Braniš, Jaroslav, Pataki, Csilla, Spörrer, Marina, Gerum, Richard C., Mainka, Astrid, Cermak, Vladimir, Goldmann, Wolfgang H., Fabry, Ben, Brabek, Jan, Rosel, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390273/
https://www.ncbi.nlm.nih.gov/pubmed/28406229
http://dx.doi.org/10.1038/srep46233
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author Braniš, Jaroslav
Pataki, Csilla
Spörrer, Marina
Gerum, Richard C.
Mainka, Astrid
Cermak, Vladimir
Goldmann, Wolfgang H.
Fabry, Ben
Brabek, Jan
Rosel, Daniel
author_facet Braniš, Jaroslav
Pataki, Csilla
Spörrer, Marina
Gerum, Richard C.
Mainka, Astrid
Cermak, Vladimir
Goldmann, Wolfgang H.
Fabry, Ben
Brabek, Jan
Rosel, Daniel
author_sort Braniš, Jaroslav
collection PubMed
description CAS is a docking protein, which was shown to act as a mechanosensor in focal adhesions. The unique assembly of structural domains in CAS is important for its function as a mechanosensor. The tension within focal adhesions is transmitted to a stretchable substrate domain of CAS by focal adhesion-targeting of SH3 and CCH domain of CAS, which anchor the CAS protein in focal adhesions. Mechanistic models of the stretching biosensor propose equal roles for both anchoring domains. Using deletion mutants and domain replacements, we have analyzed the relative importance of the focal adhesion anchoring domains on CAS localization and dynamics in focal adhesions as well as on CAS-mediated mechanotransduction. We confirmed the predicted prerequisite of the focal adhesion targeting for CAS-dependent mechanosensing and unraveled the critical importance of CAS SH3 domain in mechanosensing. We further show that CAS localizes to the force transduction layer of focal adhesions and that mechanical stress stabilizes CAS in focal adhesions.
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spelling pubmed-53902732017-04-14 The role of focal adhesion anchoring domains of CAS in mechanotransduction Braniš, Jaroslav Pataki, Csilla Spörrer, Marina Gerum, Richard C. Mainka, Astrid Cermak, Vladimir Goldmann, Wolfgang H. Fabry, Ben Brabek, Jan Rosel, Daniel Sci Rep Article CAS is a docking protein, which was shown to act as a mechanosensor in focal adhesions. The unique assembly of structural domains in CAS is important for its function as a mechanosensor. The tension within focal adhesions is transmitted to a stretchable substrate domain of CAS by focal adhesion-targeting of SH3 and CCH domain of CAS, which anchor the CAS protein in focal adhesions. Mechanistic models of the stretching biosensor propose equal roles for both anchoring domains. Using deletion mutants and domain replacements, we have analyzed the relative importance of the focal adhesion anchoring domains on CAS localization and dynamics in focal adhesions as well as on CAS-mediated mechanotransduction. We confirmed the predicted prerequisite of the focal adhesion targeting for CAS-dependent mechanosensing and unraveled the critical importance of CAS SH3 domain in mechanosensing. We further show that CAS localizes to the force transduction layer of focal adhesions and that mechanical stress stabilizes CAS in focal adhesions. Nature Publishing Group 2017-04-13 /pmc/articles/PMC5390273/ /pubmed/28406229 http://dx.doi.org/10.1038/srep46233 Text en Copyright © 2017, 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
Braniš, Jaroslav
Pataki, Csilla
Spörrer, Marina
Gerum, Richard C.
Mainka, Astrid
Cermak, Vladimir
Goldmann, Wolfgang H.
Fabry, Ben
Brabek, Jan
Rosel, Daniel
The role of focal adhesion anchoring domains of CAS in mechanotransduction
title The role of focal adhesion anchoring domains of CAS in mechanotransduction
title_full The role of focal adhesion anchoring domains of CAS in mechanotransduction
title_fullStr The role of focal adhesion anchoring domains of CAS in mechanotransduction
title_full_unstemmed The role of focal adhesion anchoring domains of CAS in mechanotransduction
title_short The role of focal adhesion anchoring domains of CAS in mechanotransduction
title_sort role of focal adhesion anchoring domains of cas in mechanotransduction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390273/
https://www.ncbi.nlm.nih.gov/pubmed/28406229
http://dx.doi.org/10.1038/srep46233
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