Regulation mechanism of Glycosphingolipids metabolism by O-GlcNACylation

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K06120
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Nagoya University (2021-2022); Kawasaki Medical School (2018-2020)
• Principal Investigator: Go Shinji 名古屋大学, 糖鎖生命コア研究所, 特任准教授 (10458218)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 糖鎖 / 糖脂質 / シアル酸 / リソソーム

Outline of Final Research Achievements

We have been analyzing the integrated regulatory mechanism of cellular glycosylation by "O-GlcNAcylation (addition of the sugar N-acetylglucosamine (GlcNAc) to serine/threonine residues of proteins)," a post-translational modification of intracellular (cytoplasmic and nuclear) proteins.
In this study, it was clarified for the first time that O-GlcNAcylation regulates the biosynthesis of glycolipids, the metabolism of sialic acid, a sugar important for glycans, and lysosomal functions involved in the catabolism (degradation) of glycans. These findings suggest that cells may use GlcNAc as a sensor to sense the status of cellular glycans and to control appropriate glycan metabolism in an integrated manner.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

これまで、糖鎖の生合成、分解は個別に研究が進められてきた。今回、GlcNAcを中心として（特にO-GlcNAc化を介して）、細胞の糖鎖代謝が統合的に連動して制御されていることを見出した。
また、GlcNAcアナログを用いた、糖鎖発現制御に関しても道筋が得られており、創薬、研究ツール開発にもつながることが期待できる。