Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex
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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.
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VE-cadherin and VEGFR2/3 can form a mechanosensitive complex in endothelial cells that controls VEGFR signaling in a shear-force-dependent manner.
“VE-cadherin and VEGFR2/3 can form a mechanosensitive complex in endothelial cells that controls VEGFR signaling in a shear-force-dependent manner45.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [45]
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Flow-mediated endothelial mechanotransduction
Davies, P. F. (1995) · Physiological Reviews · doi:10.1152/physrev.1995.75.3.519 · Cited by 2,802 · see citing works
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- Authors
- Coon, B. G., Baeyens, N., Han, J., Budatha, M., Ross, T. D., Fang, J. S., Yun, S., Thomas, J.-L., & Schwartz, M. A.
- Affiliations
- Yale University (US)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Schwartz, Martin A.
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2015-03-23
- Volume
- 208
- Issue
- 7
- Pages
- 975-986
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC4384728
- OpenAlex
- W2161020445
- Cited by
- 299
- References
- 1
- Citations by year
- 2026: 16 · 2025: 17 · 2024: 26 · 2023: 21 · 2022: 29 · 2021: 32 · 2020: 36 · 2019: 29 · 2018: 24 · 2017: 29 · 2016: 29 · 2015: 11
- FWCI
- 13.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (UL1TR000142)
- National Heart, Lung, and Blood Institute (R01HL075092, T32HL007950)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- VE-cadherin, VEGFR2, VEGFR-3, fluid shear stress, endothelial junctions, CD31, aortic endothelium, atherosclerosis, flow disturbance
- MeSH terms
- Cadherin 5, Animals, Cell Movement, Cells, Cultured, Endothelium, Vascular, Humans, Mice, Inbred C57BL, Stress, Physiological, Stress, Mechanical, Antigens, CD, Cadherins, Protein Structure, Tertiary, Neovascularization, Physiologic, Platelet Endothelial Cell Adhesion Molecule-1, RNA Interference, RNA, Small Interfering, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor Receptor-3, Mechanotransduction, Cellular, Mice, HEK293 Cells, Plaque, Atherosclerotic, Human Umbilical Vein Endothelial Cells
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