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EMBO Rep. 2016 Feb;17(2):167-77. doi: 10.15252/embr.201540789. Epub 2016 Jan 11.

NgBR is essential for endothelial cell glycosylation and vascular development.

Author information

1
Department of Pharmacology and Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA.
2
Department of Biochemistry, Duke University Medical Center, Durham, NC, USA.
3
Department of Pharmacology and Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA william.sessa@yale.edu.

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.

KEYWORDS:

NgBR; cis‐prenyltransferase; dolichol; glycosylation; vascular development

PMID:
26755743
PMCID:
PMC5290814
DOI:
10.15252/embr.201540789
[Indexed for MEDLINE]
Free PMC Article

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