Abstract
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.
| Original language | English |
|---|---|
| Article number | 1208 |
| Journal | Nature Communications |
| Volume | 3 |
| DOIs | |
| Publication status | Published - 2012 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
Cite this
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; Koh, Gou Young; Franco, Davide; Kurtcuoglu, Vartan; Poulikakos, Dimos; Baluk, Peter; McDonald, Donald; Grazia Lampugnani, Maria; Dejana, Elisabetta.
In: Nature Communications, Vol. 3, 1208, 2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo
AU - Orsenigo, Fabrizio
AU - Giampietro, Costanza
AU - Ferrari, Aldo
AU - Corada, Monica
AU - Galaup, Ariane
AU - Sigismund, Sara
AU - Ristagno, Giuseppe
AU - Maddaluno, Luigi
AU - Koh, Gou Young
AU - Franco, Davide
AU - Kurtcuoglu, Vartan
AU - Poulikakos, Dimos
AU - Baluk, Peter
AU - McDonald, Donald
AU - Grazia Lampugnani, Maria
AU - Dejana, Elisabetta
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84870688010&partnerID=8YFLogxK
U2 - 10.1038/ncomms2199
DO - 10.1038/ncomms2199
M3 - Article
C2 - 23169049
AN - SCOPUS:84870688010
VL - 3
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 1208
ER -