2020 Fiscal Year Final Research Report
Understanding of the mechanisms of sulfated glycosaminoglycan synthesis and their functions
| Project/Area Number |
17K07353
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Kobe Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Keywords | プロテオグリカン / グリコサミノグリカン / コンドロイチン硫酸 |
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| Outline of Final Research Achievements |
Proteoglycans (PGs) are cell-surface and extracellular matrix macromolecules that comprise a core protein to which glycosaminoglycan (GAG) chains are attached. The GAG moiety is essential for the PG functions. Thus, it is considered that cells are equipped with mechanisms that ensure proper GAG synthesis. Recently, Yoshida, H. et al. has reported that the TFE3 pathway allows the Golgi apparatus to regulate protein glycosylation to accommodate cellular demands. In this study, we have examined whether GAG biosynthesis is regulated by the TFE3 pathway. Overexpression of PG core proteins activated TFE3 and induced the expression of GAG biosynthetic enzymes, to sustain proper PG synthesis. In addition, we investigated the biological significance of the TFE3 pathway during neuronal differentiation. Knockdown of TFE3 inhibited neuronal differentiation. Furthermore, we found the small compound which activates TFE3.
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| Free Research Field |
糖鎖生物学
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| Academic Significance and Societal Importance of the Research Achievements |
コアタンパク質にグリコサミノグリカン (GAG) と呼ばれる直鎖状の硫酸化糖鎖が付加したプロテオグリカン (PG) は, 細胞表面や細胞外マトリクスに存在し, 細胞の増殖・分化をはじめとする種々の機能を制御する. 本研究で, コアタンパク質の合成増大に応じて GAG 鎖の合成が制御される仕組みを見出したこと, このような制御経路が神経分化過程で働いることを示したことに学術的意義がある. さらに, この制御経路に関わる転写因子の活性化を引き起こす低分子化合物を見出し, これが神経分化を促進することを明らかにした点に社会的意義がある.
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