Roles of Golgi apparatus dynamics regulated by Reelin signaling in neuronal homeostasis
| Project/Area Number |
18K06543
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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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| Review Section |
Basic Section 46030:Function of nervous system-related
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| Research Institution | Institute for Developmental Research Aichi Developmental Disability Center |
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Principal Investigator |
Matsuki Tohru 愛知県医療療育総合センター発達障害研究所, 細胞病態研究部, 主任研究員 (90332329)
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| Co-Investigator(Kenkyū-buntansha) |
中山 敦雄 愛知県医療療育総合センター発達障害研究所, 細胞病態研究部, 部長 (50227964)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | STK25 / Rac1 / RhoA / 神経細動移動 / 大脳皮質形成 / genetic compensation / MST3 / Reelin / ゴルジ体 / GM130 / PKC / 神経細胞移動 / Rho-GTPase / Reelinシグナル / ゴルジ体構造制御 / ゴルジ小胞 / 記憶・学習 / Stk25シグナル |
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| Outline of Final Research Achievements |
During cortical lamination, neuronal migration is precisely regulated and critical for functional brain development. Here we resolve the conundrum that although the acute disruption of Stk25 causes a defect in neuronal migration, constitutive Stk25-null mice have no histological aberrations. MST3, a member of the GCKIII subgroup of the Ste20-like kinase family, compensates for STK25 by playing similar roles in several biological functions. In vivo, MST3 overexpression in Stk25-knockout neurons rescued neuronal migration and axonogenesis. Mechanistically, we find that STK25 acts through the Cul3/Bacurd1 complex to activate Rac1 and degrade of RhoA, through in vivo rescue experiments. Collectively, our findings demonstrate that STK25 and MST3 have redundant roles to regulate Rho GTPases and provide a detailed link between STK25 and regulation of the actin cytoskeleton.
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| Academic Significance and Societal Importance of the Research Achievements |
大脳皮質形成時においてRho-GTPaseファミリーが重要な役割を果たしている事はこれまでに明らかにされていたが、STK25がRac1とRhoAの機能調節両方に関与する事を初めて示す事が出来た。また、今回の研究成果ではgenetic compensationについても言及しており、その代償機構の一端を明らかにする事が出来た。本成果は、genetic compensationが働いていると考えられる他の分子を研究上で重要な視点を与えるとともに、大脳皮質形成機構の解明を前進させる事に貢献できたと確信している。
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Report
(5 results)
Research Products
(11 results)
