Metabolically programmed quality control system for dolichol-linked oligosaccharides

Yoichiro Harada, Kazuki Nakajima, Yukii Masahara-Negish, Hudson H. Freeze, Takashi Angata, Naoyuki Taniguchi, Tadashi Suzuki

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The glycolipid Glc3Man9GlcNAc2- pyrophosphate-dolichol serves as the precursor for asparagine (N)-linked protein glycosylation in mammals. The biosynthesis of dolichol-linked oligosaccharides (DLOs) is arrested in low-glucose environments via unknown mechanisms, resulting in abnormal N-glycosylation. Here, we show that under glucose deprivation, DLOs are prematurely degraded during the early stages of DLO biosynthesis by pyrophosphatase, leading to the release of singly phosphorylated oligosaccharides into the cytosol. We identified that the level of GDP-mannose (Man), which serves as a donor substrate for DLO biosynthesis, is substantially reduced under glucose deprivation. We provide evidence that the selective shutdown of the GDP-Man biosynthetic pathway is sufficient to induce the release of phosphorylated oligosaccharides. These results indicate that glucoseregulated metabolic changes in the GDP-Man biosynthetic pathway cause the biosynthetic arrest of DLOs and facilitate their premature degradation by pyrophosphatase. We propose that this degradation system may avoid abnormal N-glycosylation with premature oligosaccharides under conditions that impair efficient DLO biosynthesis.

Original languageEnglish
Pages (from-to)19366-19371
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number48
DOIs
Publication statusPublished - 26-11-2013

All Science Journal Classification (ASJC) codes

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