| Project/Area Number |
17H03981
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Musashino University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
福山 征光 東京大学, 大学院薬学系研究科(薬学部), 講師 (20422389)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Keywords | DiRas / SmgGDS / RhoA / Rag / アシル基転移酵素 / Rac / GEF / 阻害剤 / Rac阻害剤 / 必須アミノ酸 / FLCN / sestrin / szt2 / 生化学 / 細胞情報伝達機構 / Ｇタンパク質 |
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| Outline of Final Research Achievements |
G proteins are central molecules that control survival and adaptation of organisms. Understanding the molecular mechanisms of their existence and regulation is expected to lead to the understanding of physiological responses and the pathogenesis of diseases caused by their malfunction. Organisms utilize the G-cycle from various aspects to respond to external stimuli. In this study, we have investigated the G-cycle of various organisms, from molds to nematodes to humans, using multifaceted analytical methods such as biochemistry, genetics, and structural biology, and have identified a novel mechanism of G-cycle activation by the smgGDS protein, the requirement of the G-protein ARL8b during embryogenesis, and a group of molecules that cause genetic interactions with the G-protein Rag. In addition, we have identified G-cycles involved in the regulation of mycelium formation in fungi.
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| Academic Significance and Societal Importance of the Research Achievements |
G蛋白質を中心とした細胞内シグナル伝達系は、多様な生物の現象に関与する。一方で、Gサイクルを制御する分子群がどのように外界からのシグナルに応じて機能するのかはまだよくわかっていませんでした。本研究では、細胞内のシグナル伝達のON/OFFを切り替える低分子量G 蛋白質を調節する分子群を同定するとともに、一部の蛋白質構造を明らかにしました。本研究は、生物のGサイクルが外的環境へと応答する精緻な機構を明らかにするとともに、疾患の発症の根底にあるGサイクルの異常を生体ホメオスタシスの維持機構という観点から解明するための基盤を提供することと期待されます。
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