Calcium signaling mediates a biphasic mechanoadaptive response of endothelial cells to cyclic mechanical stretch

Autor: Eva Faurobert, Xinping Li, Yekaterina A. Miroshnikova, Corinne Albiges-Rizo, Sara A. Wickström, Sandra Manet
Přispěvatelé: Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Max planck Institute for Biology of Ageing [Cologne], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, FRM, ANR-17-CE13-0022,CODECIDE,Coincidence de detection dans l'identité cellulaire(2017), ALBIGES-RIZO, Corinne, Coincidence de detection dans l'identité cellulaire - - CODECIDE2017 - ANR-17-CE13-0022 - AAPG2017 - VALID, University of Helsinki
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Molecular Biology of the Cell
Molecular Biology of the Cell, 2021, 32 (18), pp.1724-1736. ⟨10.1091/mbc.E21-03-0106⟩
Mol Biol Cell
Molecular Biology of the Cell, American Society for Cell Biology, 2021, 32 (18), pp.1724-1736. ⟨10.1091/mbc.E21-03-0106⟩
ISSN: 1939-4586
Popis: International audience; The vascular system is precisely regulated to adjust blood flow to organismal demand, thereby guaranteeing adequate perfusion under varying physiological conditions. Mechanical forces, such as cyclic circumferential stretch, are among the critical stimuli that dynamically adjust vessel distribution and diameter, but the precise mechanisms of adaptation to changing forces are unclear. We find that endothelial monolayers respond to cyclic stretch by transient remodeling of the vascular endothelial cadherin-based adherens junctions and the associated actomyosin cytoskeleton. Time-resolved proteomic profiling reveals that this remodeling is driven by calcium influx through the mechanosensitive Piezo1 channel, triggering Rho activation to increase actomyosin contraction. As the mechanical stimulus persists, calcium signaling is attenuated through transient down-regulation of Piezo1 protein. At the same time, filamins are phosphorylated to increase monolayer stiffness, allowing mechanoadaptation to restore junctional integrity despite continuing exposure to stretch. Collectively, this study identifies a biphasic response to cyclic stretch, consisting of an initial calcium-driven junctional mechanoresponse, followed by mechanoadaptation facilitated by monolayer stiffening.
Databáze: OpenAIRE