Role of YAP/TAZ in mechanotransduction
Top Cited Papers
- 8 June 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 474 (7350), 179-183
- https://doi.org/10.1038/nature10137
Abstract
Cells perceive their microenvironment not only through soluble signals but also through physical and mechanical cues, such as extracellular matrix (ECM) stiffness or confined adhesiveness. By mechanotransduction systems, cells translate these stimuli into biochemical signals controlling multiple aspects of cell behaviour, including growth, differentiation and cancer malignant progression, but how rigidity mechanosensing is ultimately linked to activity of nuclear transcription factors remains poorly understood. Here we report the identification of the Yorkie-homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1) as nuclear relays of mechanical signals exerted by ECM rigidity and cell shape. This regulation requires Rho GTPase activity and tension of the actomyosin cytoskeleton, but is independent of the Hippo/LATS cascade. Crucially, YAP/TAZ are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry; conversely, expression of activated YAP overrules physical constraints in dictating cell behaviour. These findings identify YAP/TAZ as sensors and mediators of mechanical cues instructed by the cellular microenvironment.This publication has 44 references indexed in Scilit:
- Integrins and Extracellular Matrix in MechanotransductionCold Spring Harbor Perspectives in Biology, 2010
- Substrate Elasticity Regulates Skeletal Muscle Stem Cell Self-Renewal in CultureScience, 2010
- Mechanical control of tissue and organ developmentDevelopment, 2010
- Linking actin dynamics and gene transcription to drive cellular motile functionsNature Reviews Molecular Cell Biology, 2010
- Matrix density-induced mechanoregulation of breast cell phenotype, signaling and gene expression through a FAK–ERK linkageOncogene, 2009
- Mechanotransduction gone awryNature Reviews Molecular Cell Biology, 2009
- Matrix Elasticity Directs Stem Cell Lineage SpecificationCell, 2006
- Local force and geometry sensing regulate cell functionsNature Reviews Molecular Cell Biology, 2006
- Cell Shape, Cytoskeletal Tension, and RhoA Regulate Stem Cell Lineage CommitmentDevelopmental Cell, 2004
- Geometric Control of Cell Life and DeathScience, 1997