Cantagrel, Vincent and Lefeber, Dirk J. and Ng, Bobby G. and Guan, Ziqiang and Silhavy, Jennifer L. and Bielas, Stephanie L. and Lehle, Ludwig and Hombauer, Hans and Adamowicz, Maciej and Swiezewska, Ewa and De Brouwer, Arjan P. and Bluemel, Peter and Sykut-Cegielska, Jolanta and Houliston, Scott and Swistun, Dominika and Ali, Bassam R. and Dobyns, William B. and Babovic-Vuksanovic, Dusica and van Bokhoven, Hans and Wevers, Ron A. and Raetz, Christian R. H. and Freeze, Hudson H. and Morava, Eva and Al-Gazali, Lihadh and Gleeson, Joseph G. (2010) SRD5A3 Is Required for Converting Polyprenol to Dolichol and Is Mutated in a Congenital Glycosylation Disorder. CELL, 142 (2). pp. 203-217. ISSN 0092-8674, 1097-4172
Full text not available from this repository. (Request a copy)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 5 alpha-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IONIZATION-MASS-SPECTROMETRY; AUTOSOMAL RECESSIVE SYNDROME; RATE-LIMITING STEP; STEROID 5-ALPHA-REDUCTASE; SACCHAROMYCES-CEREVISIAE; N-GLYCOSYLATION; RAT-LIVER; BIOSYNTHESIS; PHOSPHATE; CDG; |
| Subjects: | 500 Science > 580 Botanical sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Pflanzenwissenschaften > Lehrstuhl für Zellbiologie und Pflanzenphysiologie (Prof. Dr. Klaus Grasser) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jul 2020 06:43 |
| Last Modified: | 22 Jul 2020 06:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24451 |
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