Studies on structural fluctuation of the endoplasmic reticulum
| Project/Area Number |
17K07311
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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 |
Structural biochemistry
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
WADA IKUO 福島県立医科大学, 医学部, 教授 (40182969)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 小胞体 / 構造揺動 / 拡散 / 微小管 / ゆらぎ / 蛍光相関解析 / 分泌 / 揺らぎ / 分子混雑度 / 膜タンパク質 / フォールディング / 揺動 / タンパク質拡散 / 細胞骨格 / 高分子拡散 / 蛍光イメージング / 一分子計測 / Molecular crowding |
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| Outline of Final Research Achievements |
We analyzed microdynamics exhibited by the endoplasmic reticulum (ER) in living and semi-permeable cells. We found that the fluctuations were triggered by reactions requiring ATP or NADPH from membrane components, which were related to the softness of the ER membranes. While protein diffusion in the lumen is relatively constant over a wide range of temperature, unlike in solution, the microstructural fluctuation showed the same property. Since the motion was controlled by binding to microtubules via CLIMP-63, it is conceivable that it functions to maintain proper flow in the ER lumen. Interestingly, we found that anti-inflammatory, anti-oxidative reagent, ebselen, abolishes the micromotion of the ER. Given that ebselen traps peroxynitrite, the NADPH driven micromotion may involve related reactions.
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| Academic Significance and Societal Importance of the Research Achievements |
小胞体では分泌蛋白の新生、脂質合成、異物代謝など多くの反応をおこなう。その内腔は数十nmの厚みからなる狭い空間で、高い混雑度を持つ。この構造が示す微小な構造揺動が反応自体を進める可能性について、本研究で調べた。得られた知見から、小胞体内では反応の基盤となるタンパク質の動きは温度依存性を示さないという特性を見出し、これには構造の細かな揺れが関連し、小胞体内反応で恒常性を保持する機構と考えられる。この動きは小胞体膜自体で発生するもので、エネルギーあるいは一電子還元によって生み出されていた。またこの研究過程で多くの先端的な技法を用いたが、これらが活用されて多くの共同研究成果も得られた。
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Report
(6 results)
Research Products
(27 results)
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[Journal Article] Integrative genome analysis identified the KANNO blood group antigen as prion protein2019
Author(s)
Omae Y, Ito S, Takeuchi M, Isa K, Ogasawara K, Kawabata K, Oda A, Kaito S, Tsuneyama H, Uchikawa M, Wada I, Ohto H, Tokunaga K
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Journal Title
Transfusion
Volume: 59
Issue: 7
Pages: 2429-2435
DOI
Related Report
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