Lee, N.Y., Golzio, C., Gatza, C.E., Sharma, A., Katsanis, N., and Blobe, G.C. (2012) Endoglin Regulates PI3-Kinase/Akt Trafficking and Signaling to Alter Endothelial Capillary Stability During Angiogenesis. Molecular biology of the cell. 23(13):2412-2423.
Endoglin (CD105) is an endothelial-specific TGF-β coreceptor essential for angiogenesis and vascular homeostasis. While endoglin
dysfunction contributes to numerous vascular conditions, the mechanism of endoglin action remains poorly understood. Here
we report a novel mechanism in which endoglin and GIPC-mediated trafficking of PI3-Kinase (PI3K) regulates endothelial signaling
and function. We demonstrate that endoglin interacts with the PI3K subunits, p110α and p85, via GIPC to recruit and activate
PI3K and Akt at the cell membrane. Opposing ligand-induced effects are observed in which TGF-β1 attenuates, whereas BMP-9
enhances endoglin/GIPC-mediated membrane scaffolding of PI3K and Akt to alter endothelial capillary tube stability in vitro.
Moreover, we employ the first transgenic zebrafish model for endoglin to demonstrate that GIPC is a critical component of
endoglin function during developmental angiogenesis in vivo. These studies define a novel non-Smad function for endoglin and GIPC in regulating the endothelial cell function during