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      Endothelial cell-cell adhesion and signaling

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          Abstract

          Endothelial cells line blood vessels and provide a dynamic interface between the blood and tissues. They remodel to allow leukocytes, fluid and small molecules to enter tissues during inflammation and infections. Here we compare the signaling networks that contribute to endothelial permeability and leukocyte transendothelial migration, focusing particularly on signals mediated by small GTPases that regulate cell adhesion and the actin cytoskeleton. Rho and Rap GTPase signaling is important for both processes, but they differ in that signals are activated locally under leukocytes, whereas endothelial permeability is a wider event that affects the whole cell. Some molecules play a unique role in one of the two processes, and could therefore be targeted to selectively alter either endothelial permeability or leukocyte transendothelial migration.

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          Most cited references108

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          The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications.

          Human pathologies such as vascular malformations, hemorrhagic stroke, and edema have been associated with defects in the organization of endothelial cell junctions. Understanding the molecular basis of these diseases requires different integrated approaches which include basic cell biology, clinical studies, and studies in animal models such as mice and zebrafish. In this review we discuss recent findings derived from these approaches and their possible integration in a common picture.
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            The 'invisible hand': regulation of RHO GTPases by RHOGDIs.

            The 'invisible hand' is a term originally coined by Adam Smith in The Theory of Moral Sentiments to describe the forces of self-interest, competition and supply and demand that regulate the resources in society. This metaphor continues to be used by economists to describe the self-regulating nature of a market economy. The same metaphor can be used to describe the RHO-specific guanine nucleotide dissociation inhibitor (RHOGDI) family, which operates in the background, as an invisible hand, using similar forces to regulate the RHO GTPase cycle.
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              Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5.

              Intercellular junctions mediate adhesion and communication between adjoining cells. Although formed by different molecules, tight junctions (TJs) and adherens junctions (AJs) are functionally and structurally linked, but the signalling pathways behind this interaction are unknown. Here we describe a cell-specific mechanism of crosstalk between these two types of structure. We show that endothelial VE-cadherin at AJs upregulates the gene encoding the TJ adhesive protein claudin-5. This effect requires the release of the inhibitory activity of forkhead box factor FoxO1 and the Tcf-4-beta-catenin transcriptional repressor complex. Vascular endothelial (VE)-cadherin acts by inducing the phosphorylation of FoxO1 through Akt activation and by limiting the translocation of beta-catenin to the nucleus. These results offer a molecular basis for the link between AJs and TJs and explain why VE-cadherin inhibition may cause a marked increase in permeability.

                Author and article information

                Journal
                Exp Cell Res
                Exp. Cell Res
                Experimental Cell Research
                Academic Press
                0014-4827
                1090-2422
                01 September 2017
                01 September 2017
                : 358
                : 1
                : 31-38
                Affiliations
                [0005]Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK
                Author notes
                [* ]Corresponding author.
                Article
                S0014-4827(17)30333-6
                10.1016/j.yexcr.2017.06.003
                5700119
                28602626
                f88e5ba2-eb48-48e7-b2f0-658df353dc1b
                © 2017 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 1 June 2017
                : 2 June 2017
                Categories
                Article

                Cell biology
                endothelial cells,adherens junctions,tight junctions,rho,gtpases,rap gtpases,actin cytoskeleton,cell signaling

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