Cargando…

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

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 gro...

Descripción completa

Detalles Bibliográficos
Autores principales: Giampietro, Costanza, Disanza, Andrea, Bravi, Luca, Barrios-Rodiles, Miriam, Corada, Monica, Frittoli, Emanuela, Savorani, Cecilia, Lampugnani, Maria Grazia, Boggetti, Barbara, Niessen, Carien, Wrana, Jeff L., Scita, Giorgio, Dejana, Elisabetta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687874/
https://www.ncbi.nlm.nih.gov/pubmed/26668327
http://dx.doi.org/10.1083/jcb.201501089
_version_ 1782406683163623424
author Giampietro, Costanza
Disanza, Andrea
Bravi, Luca
Barrios-Rodiles, Miriam
Corada, Monica
Frittoli, Emanuela
Savorani, Cecilia
Lampugnani, Maria Grazia
Boggetti, Barbara
Niessen, Carien
Wrana, Jeff L.
Scita, Giorgio
Dejana, Elisabetta
author_facet Giampietro, Costanza
Disanza, Andrea
Bravi, Luca
Barrios-Rodiles, Miriam
Corada, Monica
Frittoli, Emanuela
Savorani, Cecilia
Lampugnani, Maria Grazia
Boggetti, Barbara
Niessen, Carien
Wrana, Jeff L.
Scita, Giorgio
Dejana, Elisabetta
author_sort Giampietro, Costanza
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4687874
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-46878742016-06-21 The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling Giampietro, Costanza Disanza, Andrea Bravi, Luca Barrios-Rodiles, Miriam Corada, Monica Frittoli, Emanuela Savorani, Cecilia Lampugnani, Maria Grazia Boggetti, Barbara Niessen, Carien Wrana, Jeff L. Scita, Giorgio Dejana, Elisabetta J Cell Biol Research Articles 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. The Rockefeller University Press 2015-12-21 /pmc/articles/PMC4687874/ /pubmed/26668327 http://dx.doi.org/10.1083/jcb.201501089 Text en © 2015 Giampietro et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Giampietro, Costanza
Disanza, Andrea
Bravi, Luca
Barrios-Rodiles, Miriam
Corada, Monica
Frittoli, Emanuela
Savorani, Cecilia
Lampugnani, Maria Grazia
Boggetti, Barbara
Niessen, Carien
Wrana, Jeff L.
Scita, Giorgio
Dejana, Elisabetta
The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling
title The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling
title_full The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling
title_fullStr The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling
title_full_unstemmed The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling
title_short The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling
title_sort actin-binding protein eps8 binds ve-cadherin and modulates yap localization and signaling
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687874/
https://www.ncbi.nlm.nih.gov/pubmed/26668327
http://dx.doi.org/10.1083/jcb.201501089
work_keys_str_mv AT giampietrocostanza theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT disanzaandrea theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT braviluca theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT barriosrodilesmiriam theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT coradamonica theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT frittoliemanuela theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT savoranicecilia theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT lampugnanimariagrazia theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT boggettibarbara theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT niessencarien theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT wranajeffl theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT scitagiorgio theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT dejanaelisabetta theactinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT giampietrocostanza actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT disanzaandrea actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT braviluca actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT barriosrodilesmiriam actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT coradamonica actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT frittoliemanuela actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT savoranicecilia actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT lampugnanimariagrazia actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT boggettibarbara actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT niessencarien actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT wranajeffl actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT scitagiorgio actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling
AT dejanaelisabetta actinbindingproteineps8bindsvecadherinandmodulatesyaplocalizationandsignaling