The compartmentalisation of phosphorylated free oligosaccharides in cells from a CDG Ig patient reveals a novel ER-to-cytosol translocation process.

PloS One
Delphine PericStuart E H Moore

Abstract

Biosynthesis of the dolichol linked oligosaccharide (DLO) required for protein N-glycosylation starts on the cytoplasmic face of the ER to give Man(5)GlcNAc(2)-PP-dolichol, which then flips into the ER for further glycosylation yielding mature DLO (Glc(3)Man(9)GlcNAc(2)-PP-dolichol). After transfer of Glc(3)Man(9)GlcNAc(2) onto protein, dolichol-PP is recycled to dolichol-P and reused for DLO biosynthesis. Because de novo dolichol synthesis is slow, dolichol recycling is rate limiting for protein glycosylation. Immature DLO intermediates may also be recycled by pyrophosphatase-mediated cleavage to yield dolichol-P and phosphorylated oligosaccharides (fOSGN2-P). Here, we examine fOSGN2-P generation in cells from patients with type I Congenital Disorders of Glycosylation (CDG I) in which defects in the dolichol cycle cause accumulation of immature DLO intermediates and protein hypoglycosylation. In EBV-transformed lymphoblastoid cells from CDG I patients and normal subjects a correlation exists between the quantities of metabolically radiolabeled fOSGN2-P and truncated DLO intermediates only when these two classes of compounds possess 7 or less hexose residues. Larger fOSGN2-P were difficult to detect despite an abundance of more...Continue Reading

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Citations

Nov 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yoichiro HaradaTadashi Suzuki
Oct 8, 2011·The Journal of Biological Chemistry·Isabelle ChantretStuart E H Moore
Jun 12, 2013·Biopolymers·Ritika DwivediChristine M Szymanski
May 29, 2014·Biochemical and Biophysical Research Communications·Tadashi Suzuki, Yoichiro Harada
Mar 17, 2015·Cellular and Molecular Life Sciences : CMLS·Yoichiro HaradaTadashi Suzuki
Jun 9, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ahmad MassarwehStuart E H Moore
Sep 8, 2021·The FEBS Journal·Yoichiro HaradaNaoyuki Taniguchi

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Methods Mentioned

BETA
glycosylation
FACS
ion-exchange chromatography
glucosylation
biopsy

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