TY - JOUR
T1 - Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex
AU - Coon, Brian G.
AU - Baeyens, Nicolas
AU - Han, Jinah
AU - Budatha, Madhusudhan
AU - Ross, Tyler D.
AU - Fang, Jennifer S.
AU - Yun, Sanguk
AU - Thomas, Jeon Leon
AU - Schwartz, Martin A.
N1 - Publisher Copyright:
© 2015 Coon et al.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201408103
DO - 10.1083/jcb.201408103
M3 - Article
C2 - 25800053
AN - SCOPUS:84928251808
VL - 208
SP - 975
EP - 986
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 7
ER -