Cited by 309Glycosylation and Glycoproteins ResearchGlycogen Storage Diseases and MyoclonusLysosomal Storage Disorders Research

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

Open access
Cantagrel, Vincent, Lefeber, Dirk J., Ng, Bobby G., Guan, Ziqiang, Silhavy, Jennifer L., Bielas, Stephanie L., Lehle, Ludwig, Hombauer, Hans +17 more·2010·Cell

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cell.2010.06.001

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Cantagrel, V., Lefeber, D. J., Ng, B. G., Guan, Z., Silhavy, J. L., Bielas, S. L., Lehle, L., Hombauer, H., Adamowicz, M., Swiezewska, E., De Brouwer, A. P., Blümel, P., Sykut-Cegielska, J., Houliston, S., Swistun, D., Ali, B. R., Dobyns, W. B., Babovic-Vuksanovic, D., van Bokhoven, H., Wevers, R. A., Raetz, C. R. H., Freeze, H. H., Morava, É., Al-Gazali, L., & Gleeson, J. G.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Radboud University Medical Center (NL)
  • Sanford Burnham Prebys Medical Discovery Institute (US)
  • Duke Medical Center (US)
  • University of Regensburg (DE)
  • University of California San Diego (US)
  • Children's Memorial Health Institute (PL)
  • United Arab Emirates University (AE)
  • University of Chicago (US)
Corresponding author
Gleeson, Joseph G.
Venue
Cell
Publisher
Elsevier BV
Published
2010-07
Volume
142
Issue
2
Pages
203-217
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2126181351
Cited by
309
References
65
Citations by year
2026: 11 · 2025: 10 · 2024: 16 · 2023: 16 · 2022: 12 · 2021: 22 · 2020: 26 · 2019: 13 · 2018: 19 · 2017: 18 · 2016: 14 · 2015: 17 · 2014: 22 · 2013: 18 · 2012: 30
FWCI
11.99
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
  • University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • Mayo Clinic
  • Stichting Metakids
  • Deutsche Forschungsgemeinschaft
  • National Institutes of Health (HEK293T, GM-069338, NS047101)
  • University of California, San Francisco
  • National Institute of General Medical Sciences (U54GM069338)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R24DK080506, R01DK-55615, DK-80506, R01DK055615)
  • National Institute of Neurological Disorders and Stroke (R01NS048453, R01NS052455, P30NS047101)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
SRD5A3, congenital disorders of glycosylation, N-glycosylation, polyprenols, dolichol biosynthesis, intellectual disability
MeSH terms
Abnormalities, Multiple, Animals, Butadienes, Consanguinity, Dolichols, Embryo, Mammalian, Glycosylation, Humans, Membrane Proteins, Intellectual Disability, Mutation, Pentanes, Saccharomyces cerevisiae, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Saccharomyces cerevisiae Proteins, Hemiterpenes, Mice, Genome-Wide Association Study, Unfolded Protein Response

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review