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

研究成果: Article査読

24 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)19366-19371
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
110
48
DOI
出版ステータスPublished - 26-11-2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • 一般

フィンガープリント

「Metabolically programmed quality control system for dolichol-linked oligosaccharides」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル