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

Cell 2010 Jul 15;142(2):203-17. Epub 2010 Jul 15.

Neurogenetics Laboratory, Institute for Genomic Medicine, Howard Hughes Medical Institute, Department of Neurosciences and Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2010.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940322PMC
July 2010
45 Reads

Publication Analysis

Top Keywords

n-linked glycosylation
8
pathway dolichol
4
mental retardation
4
patients mental
4
dolichol novo
4
retardation ophthalmologic
4
gene patients
4
srd5a3
4
ophthalmologic cerebellar
4
alternative pathway
4
cerebellar defects
4
srd5a3 gene
4
caused mutations
4
presence residual
4
cdg caused
4
long-sought polyprenol
4
mutations steroid
4
biosynthesis srd5a3
4
novo biosynthesis
4
type srd5a3
4

Similar Publications