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

    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 VE-cadherin 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 VE-cadherin 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 VE-cadherin. 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
    Pages (from-to)975-86
    Number of pages12
    JournalThe Journal of cell biology
    Volume208
    Issue number7
    DOIs
    Publication statusPublished - 30 Mar 2015

    Keywords

    • Animals
    • Antigens, CD
    • Antigens, CD31
    • Cadherins
    • Cell Movement
    • Cells, Cultured
    • Endothelium, Vascular
    • HEK293 Cells
    • Human Umbilical Vein Endothelial Cells
    • Humans
    • Mechanotransduction, Cellular
    • Mice
    • Mice, Inbred C57BL
    • Neovascularization, Physiologic
    • Plaque, Atherosclerotic
    • Protein Structure, Tertiary
    • RNA Interference
    • RNA, Small Interfering
    • Stress, Mechanical
    • Stress, Physiological
    • Vascular Endothelial Growth Factor Receptor-2
    • Vascular Endothelial Growth Factor Receptor-3

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