SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.
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Publication year
2010Author(s)
Source
Cell, 142, 2, (2010), pp. 203-17ISSN
Publication type
Article / Letter to editor
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Organization
Neurology
Laboratory of Genetic, Endocrine and Metabolic Diseases
Human Genetics
Paediatrics - OUD tm 2017
Journal title
Cell
Volume
vol. 142
Issue
iss. 2
Page start
p. 203
Page end
p. 17
Subject
DCN 2: Functional Neurogenomics; DCN 3: Neuroinformatics; IGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 4: Glycostation disorders; NCMLS 6: Genetics and epigenetic pathways of diseaseAbstract
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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- Academic publications [238441]
- Electronic publications [122544]
- Faculty of Medical Sciences [90373]
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