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Exploring the influence of cytosolic and membrane FAK activation on YAP/TAZ nuclear translocation

Membrane binding and unbinding dynamics play a crucial role in the biological activity of several nonintegral membrane proteins, which have to be recruited to the membrane to perform their functions. By localizing to the membrane, these proteins are able to induce downstream signal amplification in...

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Autores principales: Eroumé, Kerbaï Saïd, Cavill, Rachel, Staňková, Katerina, de Boer, Jan, Carlier, Aurélie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553670/
https://www.ncbi.nlm.nih.gov/pubmed/34509508
http://dx.doi.org/10.1016/j.bpj.2021.09.009
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author Eroumé, Kerbaï Saïd
Cavill, Rachel
Staňková, Katerina
de Boer, Jan
Carlier, Aurélie
author_facet Eroumé, Kerbaï Saïd
Cavill, Rachel
Staňková, Katerina
de Boer, Jan
Carlier, Aurélie
author_sort Eroumé, Kerbaï Saïd
collection PubMed
description Membrane binding and unbinding dynamics play a crucial role in the biological activity of several nonintegral membrane proteins, which have to be recruited to the membrane to perform their functions. By localizing to the membrane, these proteins are able to induce downstream signal amplification in their respective signaling pathways. Here, we present a 3D computational approach using reaction-diffusion equations to investigate the relation between membrane localization of focal adhesion kinase (FAK), Ras homolog family member A (RhoA), and signal amplification of the YAP/TAZ signaling pathway. Our results show that the theoretical scenarios in which FAK is membrane bound yield robust and amplified YAP/TAZ nuclear translocation signals. Moreover, we predict that the amount of YAP/TAZ nuclear translocation increases with cell spreading, confirming the experimental findings in the literature. In summary, our in silico predictions show that when the cell membrane interaction area with the underlying substrate increases, for example, through cell spreading, this leads to more encounters between membrane-bound signaling partners and downstream signal amplification. Because membrane activation is a motif common to many signaling pathways, this study has important implications for understanding the design principles of signaling networks.
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spelling pubmed-85536702022-10-19 Exploring the influence of cytosolic and membrane FAK activation on YAP/TAZ nuclear translocation Eroumé, Kerbaï Saïd Cavill, Rachel Staňková, Katerina de Boer, Jan Carlier, Aurélie Biophys J Articles Membrane binding and unbinding dynamics play a crucial role in the biological activity of several nonintegral membrane proteins, which have to be recruited to the membrane to perform their functions. By localizing to the membrane, these proteins are able to induce downstream signal amplification in their respective signaling pathways. Here, we present a 3D computational approach using reaction-diffusion equations to investigate the relation between membrane localization of focal adhesion kinase (FAK), Ras homolog family member A (RhoA), and signal amplification of the YAP/TAZ signaling pathway. Our results show that the theoretical scenarios in which FAK is membrane bound yield robust and amplified YAP/TAZ nuclear translocation signals. Moreover, we predict that the amount of YAP/TAZ nuclear translocation increases with cell spreading, confirming the experimental findings in the literature. In summary, our in silico predictions show that when the cell membrane interaction area with the underlying substrate increases, for example, through cell spreading, this leads to more encounters between membrane-bound signaling partners and downstream signal amplification. Because membrane activation is a motif common to many signaling pathways, this study has important implications for understanding the design principles of signaling networks. The Biophysical Society 2021-10-19 2021-09-10 /pmc/articles/PMC8553670/ /pubmed/34509508 http://dx.doi.org/10.1016/j.bpj.2021.09.009 Text en © 2021 Biophysical Society. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Articles
Eroumé, Kerbaï Saïd
Cavill, Rachel
Staňková, Katerina
de Boer, Jan
Carlier, Aurélie
Exploring the influence of cytosolic and membrane FAK activation on YAP/TAZ nuclear translocation
title Exploring the influence of cytosolic and membrane FAK activation on YAP/TAZ nuclear translocation
title_full Exploring the influence of cytosolic and membrane FAK activation on YAP/TAZ nuclear translocation
title_fullStr Exploring the influence of cytosolic and membrane FAK activation on YAP/TAZ nuclear translocation
title_full_unstemmed Exploring the influence of cytosolic and membrane FAK activation on YAP/TAZ nuclear translocation
title_short Exploring the influence of cytosolic and membrane FAK activation on YAP/TAZ nuclear translocation
title_sort exploring the influence of cytosolic and membrane fak activation on yap/taz nuclear translocation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553670/
https://www.ncbi.nlm.nih.gov/pubmed/34509508
http://dx.doi.org/10.1016/j.bpj.2021.09.009
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