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

Publication ,  Journal Article
Cantagrel, V; Lefeber, DJ; Ng, BG; Guan, Z; Silhavy, JL; Bielas, SL; Lehle, L; Hombauer, H; Adamowicz, M; Swiezewska, E; De Brouwer, AP ...
Published in: Cell
July 23, 2010

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.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

July 23, 2010

Volume

142

Issue

2

Start / End Page

203 / 217

Location

United States

Related Subject Headings

  • Unfolded Protein Response
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Pentanes
  • Mutation
  • Mice
  • Membrane Proteins
  • Intellectual Disability
  • Humans
  • Hemiterpenes
 

Citation

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Cantagrel, V., Lefeber, D. J., Ng, B. G., Guan, Z., Silhavy, J. L., Bielas, S. L., … Gleeson, J. G. (2010). SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell, 142(2), 203–217. https://doi.org/10.1016/j.cell.2010.06.001
Cantagrel, Vincent, Dirk J. Lefeber, Bobby G. Ng, Ziqiang Guan, Jennifer L. Silhavy, Stephanie L. Bielas, Ludwig Lehle, et al. “SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.Cell 142, no. 2 (July 23, 2010): 203–17. https://doi.org/10.1016/j.cell.2010.06.001.
Cantagrel V, Lefeber DJ, Ng BG, Guan Z, Silhavy JL, Bielas SL, et al. SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell. 2010 Jul 23;142(2):203–17.
Cantagrel, Vincent, et al. “SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.Cell, vol. 142, no. 2, July 2010, pp. 203–17. Pubmed, doi:10.1016/j.cell.2010.06.001.
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. SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell. 2010 Jul 23;142(2):203–217.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

July 23, 2010

Volume

142

Issue

2

Start / End Page

203 / 217

Location

United States

Related Subject Headings

  • Unfolded Protein Response
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Pentanes
  • Mutation
  • Mice
  • Membrane Proteins
  • Intellectual Disability
  • Humans
  • Hemiterpenes