Endothelial permeability and VE-cadherin

Gavard, Julie

doi:10.4161/cam.27330

Cited by 63 publications

(36 citation statements)

References 110 publications

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“…The adherens junction protein VE-cadherin is a endothelial-specific adhesion molecule located at junctions of ECs and responsible for barrier architecture and function. 6 VE-cadherin is a transmembrane protein that promotes homophilic interactions, forming a pericellular zipper-like structure along cell boundaries. The association of the C-terminus domain of VE-cadherin with cytoplasmic proteins is needed for its adhesive functions.…”

Section: Structure and Function Of Vascular Endothelial Adherens Juncmentioning

confidence: 99%

VE-cadherin complex plasticity: EPS8 and YAP play relay at adherens junctions

Giampietro

2016

Tissue Barriers

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The vascular endothelium is a selective barrier that separates the organs from the circulating blood. The endothelium has a wide variety of functions controlled by cell-to-cell junctions and in particular by Vascular Endothelial cadherin (VE-cadherin) complexes. Recent research identified the epidermal growth factor receptor kinase substrate 8 (EPS8) and the co-transcriptional regulator yes-associated protein (YAP) as new components of the adherens junction complexes. The binding of these 2 proteins to VE-cadherin determines the formation of different specialized adhesive structures contributing to the dynamic control of vascular permeability. This commentary will summarize what is currently known about the role of EPS8 and YAP in the modification of molecular organization and intracellular signaling of adherens junction complexes, and their potential multiple effects on vascular homeostasis. Structure and function of vascular endothelial adherens junctionsThe vascular endothelium is a highly dynamic cell layer formed by endothelial cells (ECs), a heterogeneous cell population performing essential functions in physiological and pathological processes.1,2 ECs vary in their phenotypes and in protein and surface marker expression in different tissues.3 The heterogeneity of the ECs contributes to their functional diversity at various vascular sites. 4 The organization of the junctions also differs in composition and morphological features along the vascular tree, depending on the specific permeability requirements.1,5 Endothelial tissue integrity and the establishment of cell polarity, differentiation and survival are ensured by the formation of adhesive structures between adjacent ECs.Cell-to-cell interactions are regulated by dynamic structures allowing cohesion and plasticity of organs during morphogenesis, and in the adult life. In vascular ECs, junctional complexes maintain homeostasis of blood vessels, while retaining their capacity to reorganize during angiogenesis. Both adherens and tight junction complexes, connecting adjacent cells, are characterized by a high degree of plasticity. They can rapidly respond to extracellular environmental changes, such as pro-and anti-angiogenic, and inflammatory stimuli, shear stress and blood flow inducing substantial and reversible alterations of the endothelial barrier functions. The adherens junction protein VE-cadherin is a endothelial-specific adhesion molecule located at junctions of ECs and responsible for barrier architecture and function.6 VE-cadherin is a transmembrane protein that promotes homophilic interactions, forming a pericellular zipper-like structure along cell boundaries. The association of the C-terminus domain of VE-cadherin with cytoplasmic proteins is needed for its adhesive functions.7 Through its cytoplasmic tail, VEcadherin binds both cytoskeletal and signaling proteins, which in turn allow the anchoring of cadherin to the actin microfilaments and the activation of outside-in signaling. 5,8 The association with actin is required for the ...

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Section: Structure and Function Of Vascular Endothelial Adherens Juncmentioning

confidence: 99%

VE-cadherin complex plasticity: EPS8 and YAP play relay at adherens junctions

Giampietro

2016

Tissue Barriers

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“…Phosphorylation of VE-cadherin and Its Associated Catenins Permeability-increasing agents such as VEGF, histamine, bradykinin, tumor necrosis factor, PAF, and thrombin induce phosphorylation of the VE-cadherin cytoplasmic tail and of its associated catenins, in turn leading to increased vascular permeability via VE-cadherin/catenin dissociation and VE-cadherin internalization 6,32,33 . The phosphorylation of VE-cadherin is also induced by leukocyte adhesion to endothelial cells through intercellular cell adhesion molecule-1 (ICAM-1) and is involved in diapedesis of leukocytes 3,33 .…”

Section: Regulation Of Vascular Permeability Throughmentioning

confidence: 99%

Dynamic Regulation of Vascular Permeability by Vascular Endothelial Cadherin-Mediated Endothelial Cell-Cell Junctions

2017

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Endothelial cells lining blood vessels regulate vascular barrier function, which controls the passage of plasma proteins and circulating cells across the endothelium. In most normal adult tissues, endothelial cells preserve basal vascular permeability at a low level, while they increase permeability in response to inflammation. Therefore, vascular permeability is tightly controlled by a number of extracellular stimuli and mediators to maintain tissue homeostasis. Accordingly, impaired regulation of endothelial permeability causes various diseases, including chronic inflammation, asthma, edema, sepsis, acute respiratory distress syndrome, anaphylaxis, tumor angiogenesis, and diabetic retinopathy. Vascular endothelial (VE)-cadherin, a member of the classical cadherin superfamily, is a component of cell-to-cell adherens junctions in endothelial cells and plays an important role in regulating vascular permeability. VEcadherin mediates intercellular adhesion through trans-interactions formed by its extracellular domain, while its cytoplasmic domain is anchored to the actin cytoskeleton via α-and β-catenins, leading to stabilization of VE-cadherin at cell-cell junctions. VE-cadherin-mediated cell adhesions are dynamically, but tightly, controlled by mechanisms that involve protein phosphorylation and reorganization of the actomyosin cytoskeleton. Phosphorylation of VE-cadherin, and its associated-catenins, results in dissociation of the VE-cadherin/catenin complex and internalization of VE-cadherin, leading to increased vascular permeability. Furthermore, reorganization of the actomyosin cytoskeleton by Rap1, a small GTPase that belongs to the Ras subfamily, and Rho family small GTPases, regulates VE-cadherinmediated cell adhesions to control vascular permeability. In this review, we describe recent progress in understanding the signaling mechanisms that enable dynamic regulation of VE-cadherin adhesions and vascular permeability. In addition, we discuss the possibility of novel therapeutic approaches targeting the signaling pathways controlling VE-cadherin-mediated cell adhesion in diseases associated with vascular hyper-permeability. (J Nippon Med Sch 2017; 84: 148 159)

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“…shown that disruption of VE-cadherin at endothelial cell junctions leads to a reduced endothelial barrier integrity and an increase of vascular permeability allowing the migration of inflammatory cells [301][302][303][304]. PLY causes severe pro-inflammatory activation of lung cells and is required for the development of severe pneumonia and bacterial survival in the blood [318,319].…”

Section: Alteration Of Cell Junction Proteins In Pneumococciinfected mentioning

confidence: 99%