Role of YAP/TAZ in mechanotransduction - PubMed (original) (raw)

. 2011 Jun 8;474(7350):179-83.

doi: 10.1038/nature10137.

Leonardo Morsut, Mariaceleste Aragona, Elena Enzo, Stefano Giulitti, Michelangelo Cordenonsi, Francesca Zanconato, Jimmy Le Digabel, Mattia Forcato, Silvio Bicciato, Nicola Elvassore, Stefano Piccolo

Affiliations

• PMID: 21654799
• DOI: 10.1038/nature10137

Role of YAP/TAZ in mechanotransduction

Sirio Dupont et al. Nature. 2011.

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.

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Comment in

• Mechanotransduction: YAP and TAZ feel the force.
  Wrighton KH. Wrighton KH. Nat Rev Mol Cell Biol. 2011 Jun 15;12(7):404. doi: 10.1038/nrm3136. Nat Rev Mol Cell Biol. 2011. PMID: 21673726 No abstract available.

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References

1. 1. Biochem J. 2005 May 15;388(Pt 1):217-25 - PubMed
2. 1. Nat Med. 2007 Jan;13(1):62-9 - PubMed
3. 1. Development. 2010 Aug 1;137(15):2571-8 - PubMed
4. 1. Cell. 2007 Sep 21;130(6):1120-33 - PubMed
5. 1. Cell. 2006 Aug 25;126(4):677-89 - PubMed

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