NgBR is essential for endothelial cell glycosylation and vascular development.

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Date

2016-02

Authors

Park, Eon Joo
Grabińska, Kariona A
Guan, Ziqiang
Sessa, William C

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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.

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Journal article

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NgBR, cis‐prenyltransferase, dolichol, glycosylation, vascular development, Animals, Antigens, CD31, Apoptosis, Cadherins, Cell Proliferation, Cells, Cultured, Endothelium, Vascular, Glycosylation, Mice, Protein Processing, Post-Translational, Receptors, Cell Surface, Vascular Endothelial Growth Factor Receptor-2

Citation

Published Version (Please cite this version)

10.15252/embr.201540789

Publication Info

Park, Eon Joo, Kariona A Grabińska, Ziqiang Guan and William C Sessa (2016). NgBR is essential for endothelial cell glycosylation and vascular development. EMBO Rep, 17(2). pp. 167–177. 10.15252/embr.201540789 Retrieved from https://hdl.handle.net/10161/11565.

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Scholars@Duke

Guan

Ziqiang Guan

Research Professor in Biochemistry

We develop and apply mass spectrometry techniques to address biochemical and biomedical questions that are lipid-related. Research projects include:

1) Structural lipidomics

o   Develop and apply high resolution tandem mass spectrometry-based lipidomics for the discovery, structural elucidation and functional study of novel lipids.

2) Elucidation of novel pathways/enzymes of lipid biosynthesis and metabolism

o   Genetic, biochemical and MS approaches are employed to identify the substrates and pathways involved in lipid biosynthesis and metabolism

3) Identification of lipid biomarkers of genetic diseases and cancers

o    Provide molecular insights into the disease mechanisms, as well as to serve as the diagnostic and prognostic tools of diseases.


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