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

• Published in: Nature cell biology Vol. 10; no. 8; pp. 923 - 934
• Main Authors: Taddei, Andrea, Giampietro, Costanza, Conti, Annarita, Orsenigo, Fabrizio, Breviario, Ferruccio, Pirazzoli, Valentina, Potente, Michael, Daly, Christopher, Dimmeler, Stefanie, Dejana, Elisabetta
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2008; Nature Publishing Group
• Subjects: Adherens Junctions - physiology; Adhesion; Animals; Antigens, CD - physiology; Biomedical and Life Sciences; Cadherins - physiology; Cancer Research; Cell Biology; Cell Line; Claudin-5; Developmental Biology; Endothelial Cells; Forkhead Box Protein O1; Forkhead Transcription Factors - metabolism; Genes; Genetic aspects; Humans; Kinases; Life Sciences; Membrane proteins; Membrane Proteins - genetics; Permeability; Physiological aspects; Protein kinases; Proteins; Signal Transduction; Stem Cells; TCF Transcription Factors - metabolism; Tight Junctions - genetics; Translocation; Up-Regulation - genetics; Vascular endothelium; Italy
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb1752

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–β-catenin transcriptional repressor complex. Vascular endothelial (VE)-cadherin acts by inducing the phosphorylation of FoxO1 through Akt activation and by limiting the translocation of β-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.