Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5 - PubMed (original) (raw)

doi: 10.1038/ncb1752. Epub 2008 Jul 6.

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• PMID: 18604199
• DOI: 10.1038/ncb1752

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

Andrea Taddei et al. Nat Cell Biol. 2008 Aug.

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.

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Comment in

• VE-cadherin and claudin-5: it takes two to tango.
  Gavard J, Gutkind JS. Gavard J, et al. Nat Cell Biol. 2008 Aug;10(8):883-5. doi: 10.1038/ncb0808-883. Nat Cell Biol. 2008. PMID: 18670447 Free PMC article.

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