title: NgBR is essential for endothelial cell glycosylation and vascular development.
abstract: NgBR is a transmembrane protein identified as a Nogo-B-interacting protein and recently has been shown to be a subunit required for cis-prenyltransferase (cisPTase) activity. To investigate the integrated role of NgBR in vascular development, we have characterized endothelial-specific NgBR knockout embryos. Here, we show that endothelial-specific NgBR knockout results in embryonic lethality due to vascular development defects in yolk sac and embryo proper. Loss of NgBR in endothelial cells reduces proliferation and promotes apoptosis of the cells largely through defects in the glycosylation of key endothelial proteins including VEGFR2, VE-cadherin, and CD31, and defective glycosylation can be rescued by treatment with the end product of cisPTase activity, dolichol phosphate. Moreover, NgBR functions in endothelial cells during embryogenesis are Nogo-B independent. These data uniquely show the importance of NgBR and protein glycosylation during vascular development.
authors.affiliation: Department of Pharmacology and Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Eon Joo
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Department of Pharmacology and Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Kariona A
authors.initials: KA
authors.lastname: Grabińska
authors.affiliation: Department of Biochemistry, Duke University Medical Center, Durham, NC, USA.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Guan
authors.affiliation: Department of Pharmacology and Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA william.sessa@yale.edu.
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
mesh_terms: D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D006031:Glycosylation; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D015820:Cadherins; C512615:Nogo-B receptor, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: NgBR; cis‐prenyltransferase; dolichol; glycosylation; vascular development