scholarly journals Cdc42 Regulates Adherens Junction Stability and Endothelial Permeability by Inducing α-Catenin Interaction With the Vascular Endothelial Cadherin Complex

2006 ◽  
Vol 98 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Michael T. Broman ◽  
Panos Kouklis ◽  
Xiaopei Gao ◽  
Ramaswamy Ramchandran ◽  
Radu F. Neamu ◽  
...  
Keyword(s):  
Adherens Junction ◽  
Endothelial Permeability ◽  
Vascular Endothelial ◽  
Vascular Endothelial Cadherin

scholarly journals ADAM10 Regulates Endothelial Permeability and T-Cell Transmigration by Proteolysis of Vascular Endothelial Cadherin

2008 ◽  
Vol 102 (10) ◽  
pp. 1192-1201 ◽  
Author(s):  
Beate Schulz ◽  
Jessica Pruessmeyer ◽  
Thorsten Maretzky ◽  
Andreas Ludwig ◽  
Carl P. Blobel ◽  
...  
Keyword(s):  
T Cell ◽  
Endothelial Permeability ◽  
Vascular Endothelial ◽  
Vascular Endothelial Cadherin

Protein kinase C modifications of VE-cadherin, p120, and β-catenin contribute to endothelial barrier dysregulation induced by thrombin

2003 ◽  
Vol 285 (2) ◽  
pp. L434-L442 ◽  
Author(s):  
Maria Konstantoulaki ◽  
Panos Kouklis ◽  
Asrar B. Malik
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Posttranslational Modifications ◽  
Barrier Function ◽  
Adherens Junction ◽  
Endothelial Permeability ◽  
Endothelial Barrier ◽  
Vascular Endothelial ◽  
Gap Formation ◽  
Kinase C

The adherens junction is a multiprotein complex consisting of the transmembrane vascular endothelial cadherin (VEC) and cytoplasmic catenins (p120, β-catenin, plakoglobin, α-catenin) responsible for the maintenance of endothelial barrier function. Junctional disassembly and modifications in cadherin/catenin complex lead to increased paracellular permeability of the endothelial barrier. However, the mechanisms of junctional disassembly remain unclear. In this study, we used the proinflammatory mediator thrombin to compromise the barrier function and test the hypothesis that phosphorylation-induced alterations of VEC, β-catenin, and p120 regulate junction disassembly and mediate the increased endothelial permeability response. The study showed that thrombin induced dephosphorylation of VEC, which is coupled to disassembly of cell-cell contacts, but VEC remained in aggregates at the plasma membrane. The cytoplasmic catenins dissociated from the VEC cytoplasmic domain in thin membrane projections formed in interendothelial gaps. We also showed that thrombin induced dephosphorylation of β-catenin and phosphorylation of p120. Thrombin-induced interendothelial gap formation and increased endothelial permeability were blocked by protein kinase C inhibition using chelerythrine and Gö-6976 but not by LY-379196. Chelerythrine also prevented thrombin-induced phosphorylation changes of the cadherin/catenin complex. Thus the present study links posttranslational modifications of VEC, β-catenin, and p120 to the mechanism of thrombin-induced increase in endothelial permeability.

scholarly journals p120 regulates endothelial permeability independently of its NH2 terminus and Rho binding

2011 ◽  
Vol 300 (1) ◽  
pp. H36-H48 ◽  
Author(s):  
Crystal R. Herron ◽  
Anthony M. Lowery ◽  
Patricia R. Hollister ◽  
Albert B. Reynolds ◽  
Peter A. Vincent
Keyword(s):  
Fluorescent Protein ◽  
Rho Gtpase ◽  
Adherens Junction ◽  
Endothelial Permeability ◽  
Vascular Endothelial ◽  
Hairpin Rna ◽  
P120 Catenin ◽  
Cell Monolayers ◽  
Green Fluorescent

The association of p120-catenin (p120) with the juxtamembrane domain (JMD) of vascular endothelial (VE)-cadherin is required to maintain VE-cadherin levels and transendothelial resistance (TEER) of endothelial cell monolayers. To distinguish whether decreased TEER was due to a loss of p120 and not to the decrease in VE-cadherin, we established a system in which p120 was depleted by short hairpin RNA delivered by lentivirus and VE-cadherin was restored via expression of VE-cadherin fused to green fluorescent protein (GFP). Loss of p120 resulted in decreased TEER, which was associated with decreased expression of VE-cadherin, β-catenin, plakoglobin, and α-catenin. Decreased TEER was rescued by restoration of p120 but not by the expression of VE-cadherin-GFP, despite localization of VE-cadherin-GFP at cell-cell borders. Expression of VE-cadherin-GFP restored levels of β-catenin and α-catenin but not plakoglobin, indicating that p120 may be important for recruitment of plakoglobin to the VE-cadherin complex. To evaluate the role of p120 interaction with Rho GTPase in regulating endothelial permeability, we expressed a recombinant form of p120, lacking the NH2 terminus and containing alanine substitutions, that eliminates binding of Rho to p120. Expression of this isoform restored expression of the adherens junction complex and rescued permeability as measured by TEER. These results demonstrate that p120 is required for maintaining VE-cadherin expression and TEER independently of its NH2 terminus and its role in regulating Rho.

scholarly journals MAGI-1 Is Required for Rap1 Activation upon Cell-Cell Contact and for Enhancement of Vascular Endothelial Cadherin-mediated Cell Adhesion

2006 ◽  
Vol 17 (2) ◽  
pp. 966-976 ◽  
Author(s):  
Atsuko Sakurai ◽  
Shigetomo Fukuhara ◽  
Akiko Yamagishi ◽  
Keisuke Sako ◽  
Yuji Kamioka ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adherens Junction ◽  
Small Gtpase ◽  
Cell Contact ◽  
Vascular Endothelial ◽  
Nucleotide Exchange ◽  
Cell Contacts ◽  
Vascular Endothelial Cadherin ◽  
Rap1 Activation ◽  
Cell Cell

Rap1 is a small GTPase that regulates adherens junction maturation. It remains elusive how Rap1 is activated upon cell-cell contact. We demonstrate for the first time that Rap1 is activated upon homophilic engagement of vascular endothelial cadherin (VE-cadherin) at the cell-cell contacts in living cells and that MAGI-1 is required for VE-cadherin-dependent Rap1 activation. We found that MAGI-1 localized to cell-cell contacts presumably by associating with β-catenin and that MAGI-1 bound to a guanine nucleotide exchange factor for Rap1, PDZ-GEF1. Depletion of MAGI-1 suppressed the cell-cell contact-induced Rap1 activation and the VE-cadherin-mediated cell-cell adhesion after Ca2+ switch. In addition, relocation of vinculin from cell-extracellular matrix contacts to cell-cell contacts after the Ca2+ switch was inhibited in MAGI-1-depleted cells. Furthermore, inactivation of Rap1 by overexpression of Rap1GAPII impaired the VE-cadherin-dependent cell adhesion. Collectively, MAGI-1 is important for VE-cadherin-dependent Rap1 activation upon cell-cell contact. In addition, once activated, Rap1 upon cell-cell contacts positively regulate the adherens junction formation by relocating vinculin that supports VE-cadherin-based cell adhesion.

Lipolysis products from triglyceride-rich lipoproteins increase endothelial permeability, perturb zonula occludens-1 and F-actin, and induce apoptosis

2007 ◽  
Vol 292 (6) ◽  
pp. H2745-H2753 ◽  
Author(s):  
Larissa Eiselein ◽  
Dennis W. Wilson ◽  
Michael W. Lamé ◽  
John C. Rutledge
Keyword(s):  
Endothelial Cells ◽  
Lipoprotein Lipase ◽  
Endothelial Permeability ◽  
Vascular Endothelial ◽  
Aortic Endothelial Cells ◽  
Zonula Occludens ◽  
Vascular Endothelial Cadherin ◽  
Zonula Occludens 1 ◽  
Human Aortic Endothelial Cells ◽  
Aortic Endothelial

Products generated from lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TGRL) are reported to increase endothelial layer permeability. We hypothesize that these increases in permeability result from the active rearrangement and dissolution of the junctional barrier in human aortic endothelial cells, as well as induction of the apoptotic cascade. Human aortic endothelial cells were treated with TGRL lipolysis products generated from coincubation of human TGRL plus lipoprotein lipase. Measurement of transendothelial electrical resistance demonstrated a time-dependent decrease in endothelial barrier function in response to TGRL lipolysis products. Immunofluorescent localization of zonula occludens-1 (ZO-1) showed radial rearrangement along cell borders after 1.5 h of treatment with lipolysis products. A concurrent redistribution of F-actin from the cell body to the cell margins was observed via rhodamine phalloidin staining. Immunofluorescent imaging for occludin and vascular endothelial cadherin showed that these proteins relocalize as well, although these changes are less prominent than for ZO-1. Western analysis of cells exposed to lipolysis products for 3 h revealed the fragmentation of ZO-1, a reduction in occludin, and no change of vascular endothelial cadherin. Lipolysis products also increased caspase-3 activity and induced nuclear fragmentation. Treatments did not cause oncosis in cells at any point during the incubation. These results demonstrate that TGRL lipolysis products play an important role in the regulation of endothelial permeability, the organization of the actin cytoskeleton, the localization and expression of junctional proteins, especially ZO-1, and the induction of apoptosis.

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