Nogo-B receptor is necessary for cellular dolichol biosynthesis and protein N-glycosylation

Kenneth D. Harrison, Eon Joo Park, Ningguo Gao, Andrew Kuo, Jeffrey S. Rush, Charles J. Waechter, Mark A. Lehrman, William C. Sessa

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49 Scopus citations

Abstract

Dolichol monophosphate (Dol-P) functions as an obligate glycosyl carrier lipid in protein glycosylation reactions. Dol-P is synthesized by the successive condensation of isopentenyl diphosphate (IPP), with farnesyl diphosphate catalysed by a cis-isoprenyltransferase (cis-IPTase) activity. Despite the recognition of cis-IPTase activity 40 years ago and the molecular cloning of the human cDNA encoding the mammalian enzyme, the molecular machinery responsible for regulating this activity remains incompletely understood. Here, we identify Nogo-B receptor (NgBR) as an essential component of the Dol-P biosynthetic machinery. Loss of NgBR results in a robust deficit in cis-IPTase activity and Dol-P production, leading to diminished levels of dolichol-linked oligosaccharides and a broad reduction in protein N-glycosylation. NgBR interacts with the previously identified cis-IPTase hCIT, enhances hCIT protein stability, and promotes Dol-P production. Identification of NgBR as a component of the cis-IPTase machinery yields insights into the regulation of dolichol biosynthesis.

Original languageEnglish (US)
Pages (from-to)2490-2500
Number of pages11
JournalEMBO Journal
Volume30
Issue number12
DOIs
StatePublished - May 1 2011

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Keywords

  • N-glycosylation
  • cis-IPTase
  • dolichol
  • protein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Harrison, K. D., Park, E. J., Gao, N., Kuo, A., Rush, J. S., Waechter, C. J., Lehrman, M. A., & Sessa, W. C. (2011). Nogo-B receptor is necessary for cellular dolichol biosynthesis and protein N-glycosylation. EMBO Journal, 30(12), 2490-2500. https://doi.org/10.1038/emboj.2011.147