| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
EDITORIAL FOCUS
1Center for Cardiovascular Sciences, Albany Medical College, Albany, New York 12208; and 2Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, West Virginia 26506
Submitted 3 September 2003 ; accepted in final form 5 December 2003
Interaction of p120 with juxtamembrane domain (JMD) of VE-cadherin has been implicated in regulation of endothelial cell-cell adhesion. We used a number of approaches to alter the level of p120 available for binding to VE-cadherin as a means to investigate the role of p120-VE-cadherin interaction in regulation of barrier function in confluent endothelial monolayers. Expression of an epitope-tagged fragment corresponding to JMD of VE-cadherin resulted in a decrease in endothelial barrier function as assessed by changes in albumin clearance and electrical resistance. Binding of JMD-Flag to p120 resulted in a decreased level of p120. In addition to decreasing p120 level, expression of JMD also decreased level of VE-cadherin. Expression of JMD also caused an increase in MLC phosphorylation and rearrangement of actin cytoskeleton, which, coupled with decreased cadherin, can contribute to loss of barrier function. Reducing p120 by siRNA resulted in a decrease in VE-cadherin, whereas increasing the level of p120 increased the level of VE-cadherin, demonstrating that p120 regulates the level of VE-cadherin. Overexpression of p120 was, however, associated with decreased barrier function and rearrangement of the actin cytoskeleton. Interestingly, expression of p120 was able to inhibit thrombin-induced increases in MLC phosphorylation, suggesting that p120 inhibits activation of Rho/Rho kinase pathway in endothelial cells. Excess p120 also prevented JMD-induced increases in MLC phosphorylation, correlating this phosphorylation with Rho/Rho kinase pathway. These findings show p120 plays a major role in regulating endothelial barrier function, as either a decrease or increase of p120 resulted in disruption of permeability across cell monolayers.
vascular endothelial cadherin; p120-catenin; endothelial cell permeability; 
-catenin
This article has been cited by other articles:
|
|
 |
|
  M. Guo, J. W. Breslin, M. H. Wu, C. J. Gottardi, and S. Y. Yuan VE-cadherin and {beta}-catenin binding dynamics during histamine-induced endothelial hyperpermeability Am J Physiol Cell Physiol, April 1, 2008; 294(4): C977 - C984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. A. Komarova, D. Mehta, and A. B. Malik Dual Regulation of Endothelial Junctional Permeability Sci. Signal., November 13, 2007; 2007(412): re8 - re8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Navaratna, P. G. McGuire, G. Menicucci, and A. Das Proteolytic Degradation of VE-Cadherin Alters the Blood-Retinal Barrier in Diabetes Diabetes, September 1, 2007; 56(9): 2380 - 2387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Birukova, I. Malyukova, V. Poroyko, and K. G. Birukov Paxillin-beta-catenin interactions are involved in Rac/Cdc42-mediated endothelial barrier-protective response to oxidized phospholipids Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L199 - L211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Carlile-Klusacek and V. Rizzo Endothelial cytoskeletal reorganization in response to PAR1 stimulation is mediated by membrane rafts but not caveolae Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H366 - H375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boguslavsky, I. Grosheva, E. Landau, M. Shtutman, M. Cohen, K. Arnold, E. Feinstein, B. Geiger, and A. Bershadsky p120 catenin regulates lamellipodial dynamics and cell adhesion in cooperation with cortactin PNAS, June 26, 2007; 104(26): 10882 - 10887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Sheets, J. Potempa, J. Travis, H. M. Fletcher, and C. A. Casiano Gingipains from Porphyromonas gingivalis W83 Synergistically Disrupt Endothelial Cell Adhesion and Can Induce Caspase-Independent Apoptosis. Infect. Immun., October 1, 2006; 74(10): 5667 - 5678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sakurai, S. Fukuhara, A. Yamagishi, K. Sako, Y. Kamioka, M. Masuda, Y. Nakaoka, and N. Mochizuki MAGI-1 Is Required for Rap1 Activation upon Cell-Cell Contact and for Enhancement of Vascular Endothelial Cadherin-mediated Cell Adhesion Mol. Biol. Cell, February 1, 2006; 17(2): 966 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Broman, P. Kouklis, X. Gao, R. Ramchandran, R. F. Neamu, R. D. Minshall, and A. B. Malik Cdc42 Regulates Adherens Junction Stability and Endothelial Permeability by Inducing {alpha}-Catenin Interaction With the Vascular Endothelial Cadherin Complex Circ. Res., January 6, 2006; 98(1): 73 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Trian, P.-O. Girodet, O. Ousova, R. Marthan, J. M. Tunon-de-Lara, and P. Berger RNA Interference Decreases PAR-2 Expression and Function in Human Airway Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., January 1, 2006; 34(1): 49 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Bodmer, A. English, M. Brady, K. Blackwell, K. Haxhinasto, S. Fotedar, K. Borgman, E.-W. Bai, and A. B. Moy Modeling error and stability of endothelial cytoskeletal membrane parameters based on modeling transendothelial impedance as resistor and capacitor in series Am J Physiol Cell Physiol, September 1, 2005; 289(3): C735 - C747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mehta p120: the guardian of endothelial junctional integrity Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1140 - L1142. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
