ZFIN ID: ZDB-PUB-160602-20
Mutation of Nogo-B receptor, a subunit of cis-prenyltransferase, causes a congenital disorder of glycosylation.
Park, E. J., Grabińska, K. A., Guan, Z., Stránecký, V., Hartmannová, H., Hodaňová, K., Barešová, V., Sovová, J., Jozsef, L., Ondrušková, N., Hansíková, H., Honzík, T., Zeman, J., Hůlková, H., Wen, R., Kmoch, S., Sessa, W. C.
Date: 2014
Source: Cell Metabolism 20(3): 448-457 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Dolichol/metabolism
  • Evolution, Molecular
  • Female
  • Gene Knockout Techniques
  • Glycosylation
  • Humans
  • Male
  • Metabolic Diseases/genetics*
  • Metabolic Diseases/metabolism
  • Mice
  • Molecular Sequence Data
  • Point Mutation
  • Receptors, Cell Surface/chemistry
  • Receptors, Cell Surface/genetics*
  • Receptors, Cell Surface/metabolism
  • Saccharomyces cerevisiae/chemistry
  • Saccharomyces cerevisiae/genetics
  • Saccharomyces cerevisiae/metabolism
  • Saccharomyces cerevisiae Proteins/chemistry
  • Saccharomyces cerevisiae Proteins/genetics
  • Saccharomyces cerevisiae Proteins/metabolism
  • Transferases/chemistry
  • Transferases/genetics*
  • Transferases/metabolism
PubMed: 25066056 Full text @ Cell Metab.
Dolichol is an obligate carrier of glycans for N-linked protein glycosylation, O-mannosylation, and GPI anchor biosynthesis. cis-prenyltransferase (cis-PTase) is the first enzyme committed to the synthesis of dolichol. However, the proteins responsible for mammalian cis-PTase activity have not been delineated. Here we show that Nogo-B receptor (NgBR) is a subunit required for dolichol synthesis in yeast, mice, and man. Moreover, we describe a family with a congenital disorder of glycosylation caused by a loss of function mutation in the conserved C terminus of NgBR-R290H and show that fibroblasts isolated from patients exhibit reduced dolichol profiles and enhanced accumulation of free cholesterol identically to fibroblasts from mice lacking NgBR. Mutation of NgBR-R290H in man and orthologs in yeast proves the importance of this evolutionarily conserved residue for mammalian cis-PTase activity and function. Thus, these data provide a genetic basis for the essential role of NgBR in dolichol synthesis and protein glycosylation.