PUBLICATION

Mutation of Nogo-B receptor, a subunit of cis-prenyltransferase, causes a congenital disorder of glycosylation.

Authors
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.
ID
ZDB-PUB-160602-20
Date
2014
Source
Cell Metabolism   20(3): 448-457 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Dolichols/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.
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping