Cargando…

Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo

Endothelial adherens junctions maintain vascular integrity. Arteries and veins differ in their permeability but whether organization and strength of their adherens junctions vary has not been demonstrated in vivo. Here we report that vascular endothelial cadherin, an endothelial specific adhesion pr...

Descripción completa

Detalles Bibliográficos
Autores principales: Orsenigo, Fabrizio, Giampietro, Costanza, Ferrari, Aldo, Corada, Monica, Galaup, Ariane, Sigismund, Sara, Ristagno, Giuseppe, Maddaluno, Luigi, Young Koh, Gou, Franco, Davide, Kurtcuoglu, Vartan, Poulikakos, Dimos, Baluk, Peter, McDonald, Donald, Grazia Lampugnani, Maria, Dejana, Elisabetta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514492/
https://www.ncbi.nlm.nih.gov/pubmed/23169049
http://dx.doi.org/10.1038/ncomms2199
_version_ 1782252046318043136
author Orsenigo, Fabrizio
Giampietro, Costanza
Ferrari, Aldo
Corada, Monica
Galaup, Ariane
Sigismund, Sara
Ristagno, Giuseppe
Maddaluno, Luigi
Young Koh, Gou
Franco, Davide
Kurtcuoglu, Vartan
Poulikakos, Dimos
Baluk, Peter
McDonald, Donald
Grazia Lampugnani, Maria
Dejana, Elisabetta
author_facet Orsenigo, Fabrizio
Giampietro, Costanza
Ferrari, Aldo
Corada, Monica
Galaup, Ariane
Sigismund, Sara
Ristagno, Giuseppe
Maddaluno, Luigi
Young Koh, Gou
Franco, Davide
Kurtcuoglu, Vartan
Poulikakos, Dimos
Baluk, Peter
McDonald, Donald
Grazia Lampugnani, Maria
Dejana, Elisabetta
author_sort Orsenigo, Fabrizio
collection PubMed
description Endothelial adherens junctions maintain vascular integrity. Arteries and veins differ in their permeability but whether organization and strength of their adherens junctions vary has not been demonstrated in vivo. Here we report that vascular endothelial cadherin, an endothelial specific adhesion protein located at adherens junctions, is phosphorylated in Y658 and Y685 in vivo in veins but not in arteries under resting conditions. This difference is due to shear stress-induced junctional Src activation in veins. Phosphorylated vascular endothelial-cadherin is internalized and ubiquitinated in response to permeability-increasing agents such as bradykinin and histamine. Inhibition of Src blocks vascular endothelial cadherin phosphorylation and bradykinin-induced permeability. Point mutation of Y658F and Y685F prevents vascular endothelial cadherin internalization, ubiquitination and an increase in permeability by bradykinin in vitro. Thus, phosphorylation of vascular endothelial cadherin contributes to a dynamic state of adherens junctions, but is not sufficient to increase vascular permeability in the absence of inflammatory agents.
format Online
Article
Text
id pubmed-3514492
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Nature Pub. Group
record_format MEDLINE/PubMed
spelling pubmed-35144922012-12-05 Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo Orsenigo, Fabrizio Giampietro, Costanza Ferrari, Aldo Corada, Monica Galaup, Ariane Sigismund, Sara Ristagno, Giuseppe Maddaluno, Luigi Young Koh, Gou Franco, Davide Kurtcuoglu, Vartan Poulikakos, Dimos Baluk, Peter McDonald, Donald Grazia Lampugnani, Maria Dejana, Elisabetta Nat Commun Article Endothelial adherens junctions maintain vascular integrity. Arteries and veins differ in their permeability but whether organization and strength of their adherens junctions vary has not been demonstrated in vivo. Here we report that vascular endothelial cadherin, an endothelial specific adhesion protein located at adherens junctions, is phosphorylated in Y658 and Y685 in vivo in veins but not in arteries under resting conditions. This difference is due to shear stress-induced junctional Src activation in veins. Phosphorylated vascular endothelial-cadherin is internalized and ubiquitinated in response to permeability-increasing agents such as bradykinin and histamine. Inhibition of Src blocks vascular endothelial cadherin phosphorylation and bradykinin-induced permeability. Point mutation of Y658F and Y685F prevents vascular endothelial cadherin internalization, ubiquitination and an increase in permeability by bradykinin in vitro. Thus, phosphorylation of vascular endothelial cadherin contributes to a dynamic state of adherens junctions, but is not sufficient to increase vascular permeability in the absence of inflammatory agents. Nature Pub. Group 2012-11-20 /pmc/articles/PMC3514492/ /pubmed/23169049 http://dx.doi.org/10.1038/ncomms2199 Text en Copyright © 2012, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Orsenigo, Fabrizio
Giampietro, Costanza
Ferrari, Aldo
Corada, Monica
Galaup, Ariane
Sigismund, Sara
Ristagno, Giuseppe
Maddaluno, Luigi
Young Koh, Gou
Franco, Davide
Kurtcuoglu, Vartan
Poulikakos, Dimos
Baluk, Peter
McDonald, Donald
Grazia Lampugnani, Maria
Dejana, Elisabetta
Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo
title Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo
title_full Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo
title_fullStr Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo
title_full_unstemmed Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo
title_short Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo
title_sort phosphorylation of ve-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514492/
https://www.ncbi.nlm.nih.gov/pubmed/23169049
http://dx.doi.org/10.1038/ncomms2199
work_keys_str_mv AT orsenigofabrizio phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT giampietrocostanza phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT ferrarialdo phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT coradamonica phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT galaupariane phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT sigismundsara phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT ristagnogiuseppe phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT maddalunoluigi phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT youngkohgou phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT francodavide phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT kurtcuogluvartan phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT poulikakosdimos phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT balukpeter phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT mcdonalddonald phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT grazialampugnanimaria phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo
AT dejanaelisabetta phosphorylationofvecadherinismodulatedbyhaemodynamicforcesandcontributestotheregulationofvascularpermeabilityinvivo