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Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5

Item Type:Article
Title:Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5
Creators Name:Taddei, A. and Giampietro, C. and Conti, A. and Orsenigo, F. and Breviario, F. and Pirazzoli, V. and Potente, M. and Daly, C. and Dimmeler, S. and Dejana, E.
Abstract: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.
Keywords:Adherens Junctions, Cadherins, CD Antigens, Cell Line, Claudin-5, Endothelial Cells, Forkhead Box Protein O1, Forkhead Transcription Factors, Membrane Proteins, Signal Transduction, TCF Transcription Factors, Tight Junctions, Up-Regulation, Animals
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:923-934
Date:August 2008
Official Publication:https://doi.org/10.1038/ncb1752
PubMed:View item in PubMed

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