The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling.

Autor:	Giampietro C; FIRC Institute of Molecular Oncology, 20139 Milan, Italy Dipartimento di Bioscienze, Università degli Studi di Milano, 20122 Milan, Italy costanza.giampietro@unimi.it elisabetta.dejana@ifom.eu giorgio.scita@ifom.eu., Disanza A; FIRC Institute of Molecular Oncology, 20139 Milan, Italy., Bravi L; FIRC Institute of Molecular Oncology, 20139 Milan, Italy., Barrios-Rodiles M; Center for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada., Corada M; FIRC Institute of Molecular Oncology, 20139 Milan, Italy., Frittoli E; FIRC Institute of Molecular Oncology, 20139 Milan, Italy., Savorani C; FIRC Institute of Molecular Oncology, 20139 Milan, Italy., Lampugnani MG; FIRC Institute of Molecular Oncology, 20139 Milan, Italy Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy., Boggetti B; Department of Dermatology, Cologne Excellence Cluster for Stress Responses in Ageing-Associated Diseases, Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany., Niessen C; Department of Dermatology, Cologne Excellence Cluster for Stress Responses in Ageing-Associated Diseases, Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany., Wrana JL; Center for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada., Scita G; FIRC Institute of Molecular Oncology, 20139 Milan, Italy Dipartimento di Scienze della Salute, Università degli Studi di Milano, 20122 Milan, Italy costanza.giampietro@unimi.it elisabetta.dejana@ifom.eu giorgio.scita@ifom.eu., Dejana E; FIRC Institute of Molecular Oncology, 20139 Milan, Italy Dipartimento di Bioscienze, Università degli Studi di Milano, 20122 Milan, Italy Department of Immunology, Genetics and Pathology, Uppsala University, 751 05 Uppsala, Sweden costanza.giampietro@unimi.it elisabetta.dejana@ifom.eu giorgio.scita@ifom.eu.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2015 Dec 21; Vol. 211 (6), pp. 1177-92. Date of Electronic Publication: 2015 Dec 14.
DOI:	10.1083/jcb.201501089
Abstrakt:	Vascular endothelial (VE)-cadherin transfers intracellular signals contributing to vascular hemostasis. Signaling through VE-cadherin requires association and activity of different intracellular partners. Yes-associated protein (YAP)/TAZ transcriptional cofactors are important regulators of cell growth and organ size. We show that EPS8, a signaling adapter regulating actin dynamics, is a novel partner of VE-cadherin and is able to modulate YAP activity. By biochemical and imaging approaches, we demonstrate that EPS8 associates with the VE-cadherin complex of remodeling junctions promoting YAP translocation to the nucleus and transcriptional activation. Conversely, in stabilized junctions, 14-3-3-YAP associates with the VE-cadherin complex, whereas Eps8 is excluded. Junctional association of YAP inhibits nuclear translocation and inactivates its transcriptional activity both in vitro and in vivo in Eps8-null mice. The absence of Eps8 also increases vascular permeability in vivo, but did not induce other major vascular defects. Collectively, we identified novel components of the adherens junction complex, and we introduce a novel molecular mechanism through which the VE-cadherin complex controls YAP transcriptional activity. (© 2015 Giampietro et al.)
Databáze:	MEDLINE
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