Abstract
Neurite outgrowth inhibitor‐B (Nogo‐B) is a membrane protein which is extensively expressed in multiple organs, especially in endothelial cells and vascular smooth muscle cells of blood vessels and belongs to the reticulon protein family. Notably, its specific receptor, Nogo‐B receptor (NgBR), encoded by NUS1, has been implicated in many crucial cellular processes, such as cholesterol trafficking, lipid metabolism, dolichol synthesis, protein N‐glycosylation, vascular remodelling, angiogenesis, tumorigenesis and neurodevelopment. In recent years, accumulating studies have demonstrated the statistically significant changes of NgBR expression levels in human diseases, including Niemann‐Pick type C disease, fatty liver, congenital disorders of glycosylation, persistent pulmonary hypertension of the newborn, invasive ductal breast carcinoma, malignant melanoma, non‐small cell lung carcinoma, paediatric epilepsy and Parkinson's disease. Besides, both the in vitro and in vivo studies have shown that NgBR overexpression or knockdown contribute to the alteration of various pathophysiological processes. Thus, there is a broad development potential in therapeutic strategies by modifying the expression levels of NgBR.
Highlights
Neurite outgrowth inhibitor-B (Nogo-B) was identified as a protein which highly expressed in caveolin-1 enriched micro-domains of endothelial cells (EC) and was considered as a family member of reticulons (RTN) that largely restricted to the tubular endoplasmic reticulum (ER) both in yeast and mammalian cells.[1,2,3]
Analysis of the fibroblasts isolated from Nogo-B receptor (NgBR)-R290H patients revealed a decrease in the synthesis of dolichol and an increase in free cholesterol levels, consistent with the results found in fibroblasts that isolated from NgBR-deficient mice
To further demonstrate the regulatory mechanisms of NgBR on angiogenesis, Rana et al performed experiments in embryoid body culture systems; the results indicated that NgBR homozygous knockout mice and EC-specific NgBR knockout mice are embryonically lethal with severe damage of vascular function
Summary
Nogo-B was identified as a protein which highly expressed in caveolin-1 enriched micro-domains of endothelial cells (EC) and was considered as a family member of reticulons (RTN) that largely restricted to the tubular endoplasmic reticulum (ER) both in yeast and mammalian cells.[1,2,3] Nogo-B is found in multiple organs, especially in EC and vascular smooth muscle cells (VSMC) of blood vessels.[3,4]In 2006, Miao and his colleagues identified a previously uncharacterized Nogo-B receptor (NgBR), encoding by NUS1 gene in human, binds to the amino terminus of Nogo-B (AmNogo-B).
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