Universität zu Köln

Giampietro, Costanza ORCID: 0000-0001-5229-3835, Disanza, Andrea ORCID: 0000-0001-5101-2907, Bravi, Luca, Barrios-Rodiles, Miriam, Corada, Monica ORCID: 0000-0001-8220-0871, Frittoli, Emanuela, Savorani, Cecilia, Lampugnani, Maria Grazia ORCID: 0000-0002-4802-7064, Boggetti, Barbara, Niessen, Carien, Wrana, Jeff L., Scita, Giorgio and Dejana, Elisabetta (2015). The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling. J. Cell Biol., 211 (6). S. 1177 - 1193. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Giampietro, Costanza UNSPECIFIED orcid.org/0000-0001-5229-3835 UNSPECIFIED Disanza, Andrea UNSPECIFIED orcid.org/0000-0001-5101-2907 UNSPECIFIED Bravi, Luca UNSPECIFIED UNSPECIFIED UNSPECIFIED Barrios-Rodiles, Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED Corada, Monica UNSPECIFIED orcid.org/0000-0001-8220-0871 UNSPECIFIED Frittoli, Emanuela UNSPECIFIED UNSPECIFIED UNSPECIFIED Savorani, Cecilia UNSPECIFIED UNSPECIFIED UNSPECIFIED Lampugnani, Maria Grazia UNSPECIFIED orcid.org/0000-0002-4802-7064 UNSPECIFIED Boggetti, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Niessen, Carien UNSPECIFIED UNSPECIFIED UNSPECIFIED Wrana, Jeff L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scita, Giorgio UNSPECIFIED UNSPECIFIED UNSPECIFIED Dejana, Elisabetta UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-383612
DOI:	10.1083/jcb.201501089
Journal or Publication Title:	J. Cell Biol.
Volume:	211
Number:	6
Page Range:	S. 1177 - 1193
Date:	2015
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VASCULAR ENDOTHELIAL-CADHERIN; YES-ASSOCIATED PROTEIN; HIPPO PATHWAY; CONTACT INHIBITION; ALPHA-CATENIN; GROWTH-FACTOR; CELL LINES; PERMEABILITY; JUNCTIONS; MICE Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38361