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Review
. 2008 Aug;9(8):742-7.
doi: 10.1038/embor.2008.123. Epub 2008 Jul 4.

Deciphering the functional role of endothelial junctions by using in vivo models

Daniel Nyqvist  1 , Costanza Giampietro, Elisabetta Dejana
Affiliations
Review

Deciphering the functional role of endothelial junctions by using in vivo models

Daniel Nyqvist et al. EMBO Rep. 2008 Aug.

Abstract

Endothelial cell-to-cell junctions are vital for the formation and integrity of blood vessels. The main adhesive junctional complexes in endothelial cells, adherens junctions and tight junctions, are formed by transmembrane adhesive proteins that are linked to intracellular signalling partners and cytoskeletal-binding proteins. Gene inactivation and blocking antibodies in mouse models have revealed some of the functions of the individual junctional components in vivo, and are increasing our understanding of the functional role of endothelial cell junctions in angiogenesis and vascular homeostasis. Adherens-junction organization is required for correct vascular morphogenesis during embryo development. By contrast, the data available suggest that tight-junction proteins are not essential for vascular development but are necessary for endothelial barrier function.

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Figures

Figure 1
Figure 1
Schematic representations of endothelial junction complexes. (A) Adherens junction (AJ) complex. (B) Tight junction (TJ) complex. Vascular endothelial (VE)-cadherin, and in some cases neuronal (N)-cadherin, promotes cell–cell adhesion, and binds to different intracellular partners that contribute to intracellular signalling and re-shaping of the actin cytoskeleton. α-Catenin binds to either β-catenin or actin microfilaments and promotes actin bundling. VE-protein tyrosine phosphatase (VE-PTP) associates specifically with VE-cadherin. Claudins promote cell–cell adhesion at TJs with the cooperation of other proteins such as occludin and junctional adhesion molecules (JAMs). Zonula occludens (ZO)1, ZO2 and cingulin contribute to TJ interaction with the actin cytoskeleton. Nectins and their intracellular partners, such as afadin, contribute to AJ and TJ organization. Details of the roles of each molecule are reported in the text. CASK, calcium/calmodulin-dependent serine protein kinase; ESAM, endothelial-cell-selective adhesion molecule; MAGI, membrane-associated guanylate kinase inverted; MUPP1, multi-PDZ protein 1; PAR3/6, partitioning-defective proteins; RPTPμ, receptor-like protein tyrosine phosphatase μ; SHP2, protein tyrosine phosphatase, non-receptor type 2; ZONAB, Y-box transcription factor.
None
From left: Costanza Giampietro, Daniel Nyqvist & Elisabetta Dejana
See this image and copyright information in PMC

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