Exploring the influence of cytosolic and membrane FAK activation on YAP/TAZ nuclear translocation
| Autor: | Aurélie Carlier, Katerina Staňková, Rachel Cavill, Kerbaï Saïd Eroumé, Jan de Boer |
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| Přispěvatelé: | CBITE, RS: MERLN - Cell Biology - Inspired Tissue Engineering (CBITE), Dept. of Advanced Computing Sciences, RS: FSE DACS, RS: FSE DACS Mathematics Centre Maastricht, Biointerface Science, ICMS Core, EAISI Health |
| Rok vydání: | 2021 |
| Předmět: |
RHOA
FOCAL ADHESION KINASE Biophysics TRANSDUCTION ACTIN Cell membrane Focal adhesion medicine Adaptor Proteins Signal Transducing DIFFERENTIAL LOCALIZATION biology Chemistry RHO GTPASES Biological activity Phosphoproteins DIFFUSION TRANSPORT Cell biology MODEL Cytosol medicine.anatomical_structure Membrane Membrane protein Focal Adhesion Protein-Tyrosine Kinases Trans-Activators biology.protein YAP Signal transduction VIRTUAL CELL Signal Transduction Transcription Factors |
| Zdroj: | Biophysical Journal, 120(20), 4360-4377. Cell Press Biophysical Journal, 120(20), 4360-4377. Biophysical Society |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2021.09.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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