Role of YAP/TAZ in mechanotransduction

Sirio Dupont (), Leonardo Morsut, Mariaceleste Aragona, Elena Enzo, Stefano Giulitti, Michelangelo Cordenonsi, Francesca Zanconato, Jimmy Le Digabel, Mattia Forcato, Silvio Bicciato, Nicola Elvassore and Stefano Piccolo ()
Additional contact information
Sirio Dupont: Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy
Leonardo Morsut: Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy
Mariaceleste Aragona: Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy
Elena Enzo: Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy
Stefano Giulitti: University of Padua, via Marzolo 9, 35131 Padua, Italy
Michelangelo Cordenonsi: Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy
Francesca Zanconato: Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy
Jimmy Le Digabel: Laboratoire Matière et Systèmes Complexes (MSC), Université Paris Diderot and CNRS UMR 7057, 10 rue A. Dumont et L. Duquet, 75205 Paris, France
Mattia Forcato: Center for Genome Research, University of Modena and Reggio Emilia, via G. Campi 287, 41100 Modena, Italy
Silvio Bicciato: Center for Genome Research, University of Modena and Reggio Emilia, via G. Campi 287, 41100 Modena, Italy
Nicola Elvassore: University of Padua, via Marzolo 9, 35131 Padua, Italy
Stefano Piccolo: Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy

Nature, 2011, vol. 474, issue 7350, 179-183

Abstract: 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.

Date: 2011
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DOI: 10.1038/nature10137

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