| Project/Area Number |
25221203
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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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| Research Field |
Applied biochemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
赤津 裕康 名古屋市立大学, 大学院医学研究科, 教授 (00399734)
戸田 好信 天理医療大学, 医療学部, 教授 (10444465)
長尾 耕治郎 京都大学, 大学院工学研究科, 助教 (40587325)
田中 亜路 安田女子大学, 薬学部, 講師 (60509040)
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| Co-Investigator(Renkei-kenkyūsha) |
KATO HIROAKI 京都大学, 大学院・薬学研究科, 教授 (90204487)
UESUGI MOTONARI 京都大学, 化学研究所, 教授 (10402926)
KUSUMI AKIHIRO 京都大学, 沖縄科学技術大学院大学, 教授 (50169992)
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| Project Period (FY) |
2013-05-31 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥207,480,000 (Direct Cost: ¥159,600,000、Indirect Cost: ¥47,880,000)
Fiscal Year 2017: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000)
Fiscal Year 2016: ¥38,740,000 (Direct Cost: ¥29,800,000、Indirect Cost: ¥8,940,000)
Fiscal Year 2015: ¥42,640,000 (Direct Cost: ¥32,800,000、Indirect Cost: ¥9,840,000)
Fiscal Year 2014: ¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000)
Fiscal Year 2013: ¥45,890,000 (Direct Cost: ¥35,300,000、Indirect Cost: ¥10,590,000)
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| Keywords | ABC蛋白質 / トランスポーター / コレステロール / 動脈硬化 / アルツハイマー病 / 増殖シグナル / 結晶構造解析 / iPS細胞 / 神経細胞 / 1分子生物学 / 構造生物学 / 膜環境 / 多能性幹細胞 / 阻害剤 / 中枢神経細胞 / 3次元構造解析 |
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| Outline of Final Research Achievements |
ATP Binding Cassette (ABC) proteins play important physiological roles through transporting hydrophobic substances, and defects in their functions are related to various diseases. In this project, we tried to reveal the functional mechanisms and physiological roles of ABC proteins involved in cholesterol homeostasis. By integrating biochemical/cell biological studies, single molecule tracking and crystal structure analyses, we proposed the novel mechanism of HDL (so-called good cholesterol) generation, in which ABCA1 directly loads excess cholesterol onto apolipoprotein A-I. Furthermore, we revealed that ABCA1 is involved in the uneven distribution of cholesterol in the plasma membrane and the modulation of cell growth signaling. We also succeeded in establishing the platform of ABC protein research by revealing the functional mechanism of multidrug exporter ABCB1 based on detailed structure analyses.
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| Assessment Rating |
Verification Result (Rating)
A+
Result (Rating)
A+: Progress in the research exceeds the initial goal. More than expected research results are expected.
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