Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex

Brian G. Coon, Nicolas Baeyens, Jinah Han, Madhusudhan Budatha, Tyler D. Ross, Jennifer S. Fang, Sanguk Yun, Jeon Leon Thomas, Martin A. Schwartz

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

Endothelial responses to fluid shear stress are essential for vascular development and physiology, and determine the formation of atherosclerotic plaques at regions of disturbed flow. Previous work identified VEcadherin as an essential component, along with PECAM-1 and VEGFR2, of a complex that mediates flow signaling. However, VE-cadherin's precise role is poorly understood. We now show that the transmembrane domain of VEcadherin mediates an essential adapter function by binding directly to the transmembrane domain of VEGFR2, as well as VEGFR3, which we now identify as another component of the junctional mechanosensory complex. VEGFR2 and VEGFR3 signal redundantly downstream of VEcadherin. Furthermore, VEGFR3 expression is observed in the aortic endothelium, where it contributes to flow responses in vivo. In summary, this study identifies a novel adapter function for VE-cadherin mediated by transmembrane domain association with VEGFRs.

Original languageEnglish (US)
Pages (from-to)975-986
Number of pages12
JournalJournal of Cell Biology
Volume208
Issue number7
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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