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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Park, EJ; Grabińska, KA; 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, WC

Published Date

  • September 2, 2014

Published In

Volume / Issue

  • 20 / 3

Start / End Page

  • 448 - 457

PubMed ID

  • 25066056

Pubmed Central ID

  • PMC4161961

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2014.06.016


  • eng

Conference Location

  • United States