Spatiotemporal model of cellular mechanotransduction via Rho and YAP.

Autor:	Novev JK; Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen Ø, Denmark., Heltberg ML; Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen Ø, Denmark.; Laboratoire de Physique, Ecole Normale Superieure, Rue Lhomond 15, Paris 07505, France., Jensen MH; Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen Ø, Denmark., Doostmohammadi A; Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen Ø, Denmark.
Jazyk:	angličtina
Zdroj:	Integrative biology : quantitative biosciences from nano to macro [Integr Biol (Camb)] 2021 Aug 12; Vol. 13 (8), pp. 197-209.
DOI:	10.1093/intbio/zyab012
Abstrakt:	How cells sense and respond to mechanical stimuli remains an open question. Recent advances have identified the translocation of Yes-associated protein (YAP) between nucleus and cytoplasm as a central mechanism for sensing mechanical forces and regulating mechanotransduction. We formulate a spatiotemporal model of the mechanotransduction signalling pathway that includes coupling of YAP with the cell force-generation machinery through the Rho family of GTPases. Considering the active and inactive forms of a single Rho protein (GTP/GDP-bound) and of YAP (non-phosphorylated/phosphorylated), we study the cross-talk between cell polarization due to active Rho and YAP activation through its nuclear localization. For fixed mechanical stimuli, our model predicts stationary nuclear-to-cytoplasmic YAP ratios consistent with experimental data at varying adhesive cell area. We further predict damped and even sustained oscillations in the YAP nuclear-to-cytoplasmic ratio by accounting for recently reported positive and negative YAP-Rho feedback. Extending the framework to time-varying mechanical stimuli that simulate cyclic stretching and compression, we show that the YAP nuclear-to-cytoplasmic ratio's time dependence follows that of the cyclic mechanical stimulus. The model presents one of the first frameworks for understanding spatiotemporal YAP mechanotransduction, providing several predictions of possible YAP localization dynamics, and suggesting new directions for experimental and theoretical studies. (© The Author(s) 2021. Published by Oxford University Press.)
Databáze:	MEDLINE
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