Reconstitution of the molecular machinery of intracellular membrane tethering and fusion
| Project/Area Number |
17K07386
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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 |
Cell biology
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| Research Institution | Osaka University |
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Principal Investigator |
Mima Joji 大阪大学, 蛋白質研究所, 准教授 (30335301)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 膜交通 / 小胞輸送 / 膜融合 / 膜テザリング / Rab / SNARE / 低分子量Gタンパク質 / 細胞内膜交通 / 細胞内小胞輸送 / Small GTPase / 再構成 / プロテオリポソーム / メンブレントラフィック / Rab GTPase / small GTPase |
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| Outline of Final Research Achievements |
Membrane tethering and fusion processes are a highly regulated event that occurs during the physical contact and merging between transport carriers and target membrane compartments, thereby ensuring the spatiotemporal specificity of intracellular membrane trafficking. Nevertheless, how essential protein components, such as SNARE-family proteins and Rab-family small GTPases, directly act upon the tethering and fusion events remains enigmatic. Here, we investigated the molecular basis of membrane tethering and fusion by comprehensively and quantitatively evaluating the intrinsic capacities of representative human Rab-family proteins and yeast SNARE-family proteins to physically tether or fuse two distinct membranes in a chemically defined reconstitution system. Comprehensive reconstitution experiments provided novel mechanistic insights into Rab-mediated membrane tethering and SNARE-mediated membrane fusion reactions.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒト細胞を含め全ての真核細胞は複雑な内膜系をもち、多種多様な物質を、各オルガネラや細胞外へと選択的に運搬している。この時空間的に高度に制御された細胞内物質輸送は、細胞内膜交通・小胞輸送と称され、正常な細胞機能に必要不可欠である。さらに、膜交通の必須因子で、本課題で対象とするRabおよびSNAREタンパク質群は、近年、ガンや神経変性疾患など、様々な疾病・疾患の発症に関与することも報告されている。本課題では、世界初の独自開発したヒト Rab再構成プロテオリポソーム解析系をはじめ、再構成アプローチを駆使することで、独創的な基礎研究の成果を生み出している。
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Report
(4 results)
Research Products
(10 results)
