SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.

Journal Article (Journal Article)

N-linked glycosylation is the most frequent modification of secreted and membrane-bound proteins in eukaryotic cells, disruption of which is the basis of the congenital disorders of glycosylation (CDGs). We describe a new type of CDG caused by mutations in the steroid 5alpha-reductase type 3 (SRD5A3) gene. Patients have mental retardation and ophthalmologic and cerebellar defects. We found that SRD5A3 is necessary for the reduction of the alpha-isoprene unit of polyprenols to form dolichols, required for synthesis of dolichol-linked monosaccharides, and the oligosaccharide precursor used for N-glycosylation. The presence of residual dolichol in cells depleted for this enzyme suggests the existence of an unexpected alternative pathway for dolichol de novo biosynthesis. Our results thus suggest that SRD5A3 is likely to be the long-sought polyprenol reductase and reveal the genetic basis of one of the earliest steps in protein N-linked glycosylation.

Full Text

Duke Authors

Cited Authors

  • Cantagrel, V; Lefeber, DJ; Ng, BG; Guan, Z; Silhavy, JL; Bielas, SL; Lehle, L; Hombauer, H; Adamowicz, M; Swiezewska, E; De Brouwer, AP; Blümel, P; Sykut-Cegielska, J; Houliston, S; Swistun, D; Ali, BR; Dobyns, WB; Babovic-Vuksanovic, D; van Bokhoven, H; Wevers, RA; Raetz, CRH; Freeze, HH; Morava, E; Al-Gazali, L; Gleeson, JG

Published Date

  • July 23, 2010

Published In

Volume / Issue

  • 142 / 2

Start / End Page

  • 203 - 217

PubMed ID

  • 20637498

Pubmed Central ID

  • PMC2940322

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2010.06.001


  • eng

Conference Location

  • United States