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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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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 |
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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 |
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