Role of Endothelial Cell–Cell Junctions in Endothelial Permeability

2011 ◽  
pp. 265-279 ◽  
Author(s):  
Armelle Le Guelte ◽  
Julie Gavard
Keyword(s):  
Endothelial Cell ◽  
Endothelial Permeability ◽  
Cell Junctions ◽  
Cell Cell

ROLE OF CELL-CELL JUNCTIONS IN MEDIATING ENDOTHELIAL CELL RESPONSES TO FLUID SHEAR STRESS

2004 ◽  
Vol 13 (3) ◽  
pp. 41
Author(s):  
Eleni Tzima ◽  
Mohamed Irani-Tehrani ◽  
Elizabetta Dejana ◽  
Martin Schwartz
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Fluid Shear Stress ◽  
Cell Junctions ◽  
Fluid Shear ◽  
Cell Responses ◽  
Cell Cell

scholarly journals Golgi-associated cPLA2α Regulates Endothelial Cell–Cell Junction Integrity by Controlling the Trafficking of Transmembrane Junction Proteins

2009 ◽  
Vol 20 (19) ◽  
pp. 4225-4234 ◽  
Author(s):  
Elsa Regan-Klapisz ◽  
Vincent Krouwer ◽  
Miriam Langelaar-Makkinje ◽  
Laxman Nallan ◽  
Michael Gelb ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Intracellular Trafficking ◽  
Adherens Junction ◽  
Cell Junctions ◽  
Cell Junction ◽  
Tight Junction Formation ◽  
Junction Formation ◽  
Junction Proteins ◽  
Cell Cell

In endothelial cells specifically, cPLA2α translocates from the cytoplasm to the Golgi complex in response to cell confluence. Considering the link between confluence and cell–cell junction formation, and the emerging role of cPLA2α in intracellular trafficking, we tested whether Golgi-associated cPLA2α is involved in the trafficking of junction proteins. Here, we show that the redistribution of cPLA2α from the cytoplasm to the Golgi correlates with adherens junction maturation and occurs before tight junction formation. Disruption of adherens junctions using a blocking anti-VE-cadherin antibody reverses the association of cPLA2α with the Golgi. Silencing of cPLA2α and inhibition of cPLA2α enzymatic activity using various inhibitors result in the diminished presence of the transmembrane junction proteins VE-cadherin, occludin, and claudin-5 at cell–cell contacts, and in their accumulation at the Golgi. Altogether, our data support the idea that VE-cadherin triggers the relocation of cPLA2α to the Golgi and that in turn, Golgi-associated cPLA2α regulates the transport of transmembrane junction proteins through or from the Golgi, thereby controlling the integrity of endothelial cell–cell junctions.

Signal transduction and regulation of lung endothelial cell permeability. Interaction between calcium and cAMP

1998 ◽  
Vol 275 (2) ◽  
pp. L203-L222 ◽  
Author(s):  
Timothy M. Moore ◽  
Paul M. Chetham ◽  
John J. Kelly ◽  
Troy Stevens
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Intracellular Signaling ◽  
Endothelial Permeability ◽  
Cell Permeability ◽  
Gap Formation ◽  
Pulmonary Endothelium ◽  
Intracellular Signals ◽  
Endothelial Cell Permeability ◽  
Cell Cell

Pulmonary endothelium forms a semiselective barrier that regulates fluid balance and leukocyte trafficking. During the course of lung inflammation, neurohumoral mediators and oxidants act on endothelial cells to induce intercellular gaps permissive for transudation of proteinaceous fluid from blood into the interstitium. Intracellular signals activated by neurohumoral mediators and oxidants that evoke intercellular gap formation are incompletely understood. Cytosolic Ca2+ concentration ([Ca2+]i) and cAMP are two signals that importantly dictate cell-cell apposition. Although increased [Ca2+]ipromotes disruption of the macrovascular endothelial cell barrier, increased cAMP enhances endothelial barrier function. Furthermore, during the course of inflammation, elevated endothelial cell [Ca2+]idecreases cAMP to facilitate intercellular gap formation. Given the significance of both [Ca2+]iand cAMP in mediating cell-cell apposition, this review addresses potential sites of cross talk between these two intracellular signaling pathways. Emerging data also indicate that endothelial cells derived from different vascular sites within the pulmonary circulation exhibit distinct sensitivities to permeability-inducing stimuli; that is, elevated [Ca2+]ipromotes macrovascular but not microvascular barrier disruption. Thus this review also considers the roles of [Ca2+]iand cAMP in mediating site-specific alterations in endothelial permeability.

scholarly journals Angiomotin Regulates Endothelial Cell-Cell Junctions and Cell Motility

2005 ◽  
Vol 280 (41) ◽  
pp. 34859-34869 ◽  
Author(s):  
Anders Bratt ◽  
Olivier Birot ◽  
Indranil Sinha ◽  
Niina Veitonmäki ◽  
Karin Aase ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Motility ◽  
Cell Junctions ◽  
Cell Cell

scholarly journals Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier

2008 ◽  
Vol 6 (3) ◽  
pp. 179-192 ◽  
Author(s):  
Svetlana Stamatovic ◽  
Richard Keep ◽  
Anuska Andjelkovic
Keyword(s):  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Cell Junctions ◽  
Brain Barrier ◽  
Brain Endothelial Cell ◽  
Blood Brain ◽  
Cell Cell

Involvement of Ca2+ in the H2O2-induced increase in endothelial permeability

1996 ◽  
Vol 270 (6) ◽  
pp. L973-L978 ◽  
Author(s):  
A. Siflinger-Birnboim ◽  
H. Lum ◽  
P. J. Del Vecchio ◽  
A. B. Malik
Keyword(s):  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Binding Sites ◽  
Endothelial Permeability ◽  
Extracellular Medium ◽  
Critical Determinant ◽  
Cell Monolayers ◽  
Sensitive Membrane

We studied the role of Ca2+ in mediating the hydrogen peroxide (H2O2)-induced increase in endothelial permeability to 125I-labeled albumin using bovine pulmonary microvessel endothelial cells (BMVEC). Changes in cytosolic-free Ca2+ ([Ca2+]i) were monitored in BMVEC monolayers loaded with the Ca(2+)-sensitive membrane permeant fluorescent dye fura 2-AM. H2O2 (100 microM) produced a rise in [Ca2+]i within 10 s that was reduced by the addition of EGTA to the medium. Uptake of 45Ca2+ from the extracellular medium increased in the presence of H2O2 (100 microM) compared with control monolayers, suggesting that the H2O2-induced rise in [Ca2+]i is partly the result of extracellular Ca2+ influx. The effects of [Ca2+]i on endothelial permeability were addressed by pretreatment of BMVEC monolayers with BAPTA-AM (3-5 microM), a membrane permeant Ca2+ chelator, before the H2O2 exposure. BAPTA-AM produced an approximately 50% decrease in the H2O2-induced increase in endothelial permeability compared with endothelial cell monolayers exposed to H2O2 alone. The increase in endothelial permeability was independent of Ca2+ influx, since LaCl3 (0-100 microM), which displaces Ca2+ from binding sites on the cell surface, did not modify the permeability response. These results indicate that the rise in [Ca2+]i produced by H2O2 is a critical determinant of the increase in endothelial permeability.

scholarly journals Rap1 Is Involved in Angiopoietin-1-Induced Cell-Cell Junction Stabilization and Endothelial Cell Sprouting

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 155
Author(s):  
Vanda Gaonac’h-Lovejoy ◽  
Cécile Boscher ◽  
Chantal Delisle ◽  
Jean-Philippe Gratton
Keyword(s):  
Endothelial Cell ◽  
Endothelial Permeability ◽  
Intercellular Junctions ◽  
Small Gtpase ◽  
Endothelial Barrier ◽  
Cell Junction ◽  
Barrier Integrity ◽  
Rap1 Activation ◽  
Angiopoietin 1 ◽  
Cell Cell

Angiopoietin-1 (Ang-1) is an important proangiogenic factor also involved in the maintenance of endothelial-barrier integrity. The small GTPase Rap1 is involved in the regulation of adherens junctions through VE-cadherin-mediated adhesion, and in endothelial permeability. While many studies established that Rap1 activation is critical for endothelial cell–cell adhesions, its roles in the antipermeability effects of Ang-1 are ill-defined. Thus, we determined the contribution of Rap1 to Ang-1-stimulated angiogenic effects on endothelial cells (ECs). We found that Rap1 is activated following Ang-1 stimulation and is required for the antipermeability effects of Ang-1 on EC monolayers. Our results also revealed that Rap1 is necessary for EC sprouting stimulated by Ang-1 but had no significant effect on Ang-1-induced EC migration and adhesion. In contrast, downregulation of VE-cadherin markedly increased the adhesiveness of ECs to the substratum, which resulted in inhibition of Ang-1-stimulated migration. These results revealed that Rap1 is central to the effects of Ang-1 at intercellular junctions of ECs, whereas VE-cadherin is also involved in the adhesion of ECs to the extracellular matrix.

scholarly journals A mechanism of Rap1-induced stabilization of endothelial cell–cell junctions

2011 ◽  
Vol 22 (14) ◽  
pp. 2509-2519 ◽  
Author(s):  
Jian J. Liu ◽  
Rebecca A. Stockton ◽  
Alexandre R. Gingras ◽  
Ararat J. Ablooglu ◽  
Jaewon Han ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Small Gtpases ◽  
Cell Junctions ◽  
Physical Interaction ◽  
Dependent Manner ◽  
Cardiovascular Development ◽  
Cavernous Malformations ◽  
Cell Cell

Activation of Rap1 small GTPases stabilizes cell–cell junctions, and this activity requires Krev Interaction Trapped gene 1 (KRIT1). Loss of KRIT1 disrupts cardiovascular development and causes autosomal dominant familial cerebral cavernous malformations. Here we report that native KRIT1 protein binds the effector loop of Rap1A but not H-Ras in a GTP-dependent manner, establishing that it is an authentic Rap1-specific effector. By modeling the KRIT1–Rap1 interface we designed a well-folded KRIT1 mutant that exhibited a ∼40-fold-reduced affinity for Rap1A and maintained other KRIT1-binding functions. Direct binding of KRIT1 to Rap1 stabilized endothelial cell–cell junctions in vitro and was required for cardiovascular development in vivo. Mechanistically, Rap1 binding released KRIT1 from microtubules, enabling it to locate to cell–cell junctions, where it suppressed Rho kinase signaling and stabilized the junctions. These studies establish that the direct physical interaction of Rap1 with KRIT1 enables the translocation of microtubule-sequestered KRIT1 to junctions, thereby supporting junctional integrity and cardiovascular development.

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