@article {1517186,
	title = {Elements of the Endomucin Extracellular Domain Essential for VEGF-Induced VEGFR2 Activity},
	journal = {Cells},
	volume = {9},
	number = {6},
	year = {2020},
	month = {2020 Jun 05},
	abstract = {Endomucin (EMCN) is the type I transmembrane glycoprotein, mucin-like component of the endothelial cell glycocalyx. We have previously shown that EMCN is necessary for vascular endothelial growth factor (VEGF)-induced VEGF receptor 2 (VEGFR2) internalization and downstream signaling. To explore the structural components of EMCN that are necessary for its function and the molecular mechanism of EMCN in VEGF-induced endothelial functions, we generated a series of mouse EMCN truncation mutants and examined their ability to rescue VEGF-induced endothelial functions in human primary endothelial cells (EC) in which endogenous EMCN had been knocked down using siRNA. Expression of the mouse full-length EMCN (FL EMCN) and the extracellular domain truncation mutants ∆21-81 EMCN and ∆21-121 EMCN, but not the shortest mutant ∆21-161 EMCN, successfully rescued the VEGF-induced EC migration, tube formation, and proliferation. ∆21-161 EMCN failed to interact with VEGFR2 and did not facilitate VEGFR2 internalization. Deletion of COSMC (C1GalT1C1) revealed that the abundant mucin-type -glycans were not required for its VEGFR2-related functions. Mutation of the two -glycosylation sites on ∆21-121 EMCN abolished its interaction with VEGFR2 and its function in VEGFR2 internalization. These results reveal ∆21-121 EMCN as the minimal extracellular domain sufficient for VEGFR2-mediated endothelial function and demonstrate an important role for -glycosylation in VEGFR2 interaction, internalization, and angiogenic activity.},
	issn = {2073-4409},
	doi = {10.3390/cells9061413},
	author = {Hu, Zhengping and Cano, Issahy and Saez-Torres, Kahira L and LeBlanc, Michelle E and Saint-Geniez, Magali and Ng, Yin-Shan and Arg{\"u}eso, Pablo and D{\textquoteright}Amore, Patricia A}
}
