| Project/Area Number |
18H05269
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Review Section |
Broad Section F
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| Research Institution | Kyoto University |
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Principal Investigator |
Ueda Kazumitsu 京都大学, 高等研究院, 特定教授 (10151789)
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| Co-Investigator(Kenkyū-buntansha) |
木村 泰久 京都大学, 農学研究科, 准教授 (10415143)
笠井 倫志 岐阜大学, 糖鎖生命コア研究所, 特任准教授 (20447949)
古寺 哲幸 金沢大学, ナノ生命科学研究所, 教授 (30584635)
中津 亨 和歌山県立医科大学, 薬学部, 教授 (50293949)
木下 政人 京都大学, 農学研究科, 准教授 (60263125)
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| Project Period (FY) |
2018-06-11 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥193,570,000 (Direct Cost: ¥148,900,000、Indirect Cost: ¥44,670,000)
Fiscal Year 2022: ¥35,620,000 (Direct Cost: ¥27,400,000、Indirect Cost: ¥8,220,000)
Fiscal Year 2021: ¥36,140,000 (Direct Cost: ¥27,800,000、Indirect Cost: ¥8,340,000)
Fiscal Year 2020: ¥36,140,000 (Direct Cost: ¥27,800,000、Indirect Cost: ¥8,340,000)
Fiscal Year 2019: ¥40,040,000 (Direct Cost: ¥30,800,000、Indirect Cost: ¥9,240,000)
Fiscal Year 2018: ¥45,630,000 (Direct Cost: ¥35,100,000、Indirect Cost: ¥10,530,000)
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| Keywords | ABC蛋白質 / コレステロール / HDL / 動脈硬化症 / 精神疾患 / 不妊 / ABCA1 / 輸送酵素 / 細胞内輸送 / Aster-A / 細胞膜ー小胞体コンタクトサイト / メダカ / 生殖反応 / 動脈硬化 / Aster / ABCA13 / 統合失調症 / 神経細胞 / ノックアウトマウス / トランスポーター / 細胞接着 / アルツハイマー病 / 神経変性疾患 / 構造解析 |
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| Outline of Final Research Achievements |
This study aimed to elucidate the function and physiological role of ABC proteins involved in cholesterol transport. As a result, multiple ABC proteins including ABCA1 were found to create a cholesterol concentration gradient across the lipid bilayer of the cell membrane of mammalian cells, and this was revealed to be important for intracellular cholesterol homeostasis. Furthermore, the functional abnormalities of ABC proteins involved in cholesterol transport were found to potentially be related to cellular functions such as cell motility, as well as diseases such as mental disorders and reproductive activities in females, suggesting that cholesterol in the cell membrane participates in the regulation of signal transmission from the extracellular space.
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| Academic Significance and Societal Importance of the Research Achievements |
高密度リポ蛋白質(HDL)は、抗動脈硬化効果をもつとされ、善玉コレステロールと呼ばれてきた。そして、ABCA1の生理的役割はHDLを産生することだと信じられてきた。本研究は、ABCA1の生理的役割が細胞膜脂質二重層間にコレステロール濃度勾配を作り出すことであることを明らかにし、コレステロールおよびHDLの生理的役割を根本から見直す必要があることを示した。本研究で得られた知見は、動脈硬化、自己免疫疾患、糖尿病、がん、アルツハイマー病、精神疾患、不妊など、さまざまな病気の予防や治療に役立つと期待される。
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| Assessment Rating |
Ex-post Assessment Comments (Rating)
A: In light of the aim of introducing the research area into the research categories, expected outcomes of research have been produced.
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Assessment Rating |
Interim Assessment Comments (Rating)
A: In light of the aim of introducing the research area into the research categories, the expected progress has been made in research.
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