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

Kerbaï Saïd Eroumé, Rachel Cavill, Katerina Staňková, Jan de Boer, Aurélie Carlier

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Membrane binding and unbinding dynamics play a crucial role in the biological activity of several non-integral membrane proteins, which have to be recruited to the membrane in order 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. Since membrane activation is a motif common to many signaling pathways, this study has important implications for understanding the design principles of signaling networks.

Original languageEnglish
JournalBiophysical Journal
DOIs
Publication statusE-pub ahead of print - 9 Sep 2021

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