| 研究課題/領域番号 |
23KJ1280
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| 研究種目 |
特別研究員奨励費
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| 配分区分 | 基金 |
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| 応募区分 | 国内 |
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| 審査区分 |
小区分46010:神経科学一般関連
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| 研究機関 | 京都大学 |
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研究代表者 |
ZHOU CHUYING 京都大学, 高等研究院, 特別研究員(DC2)
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| 研究期間 (年度) |
2023-04-25 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
1,800千円 (直接経費: 1,800千円)
2024年度: 900千円 (直接経費: 900千円)
2023年度: 900千円 (直接経費: 900千円)
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| キーワード | Nesprin-2 / Dynein / Kinesin-1 / Nucleus / Neuronal migration |
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| 研究開始時の研究の概要 |
During mammalian brain development, neurons undergo active migration, accompanied with forward movements of the nuclei. This study aims to reveal how a nuclear membrane protein, Nesprin-2 generates forward neuronal nuclear movements by coordinated the activities of opposing microtubule motors, dynein and kinesin-1. By advanced live-cell imaging techniques and a thorough analysis of Nesprin-2-mediated intracellular cargo dynamics, a mechanistic understanding on the neuronal nuclear dynamics will be achieved, offering new insights into neurodevelopmental diseases.
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| 研究実績の概要 |
My major achievements are as followed: (1) biochemical experiments were performed to further analyze how Nesprin-2 binds to dynein complexes by utilizing a BicD2 stable knockout cell line, (2) protein structure prediction was used to understand the 3D conformation of Nesprin-2 protein, which shows an atypical arrangement of dynein-dynactin-binding motifs, (3) rescue experiments were performed using Nesprin-2 knockout cells and expected results were obtained, showing that binding to both microtubule motors is sufficient for the recovery of nuclear movements (4) movements of microtubules in migrating neurons were analyzed by photo-conversion experiments. Taken together, our results provide further insights into the role of Nesprin-2 as a coordinating adaptor for smooth nuclear transport.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Although some modifications of experiment plan were made, the project overall is progressing smoothly.
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| 今後の研究の推進方策 |
During the current fiscal year, I found that Nesprin-2 drives active bidirectional movements over a prolonged period and keeps the cargo at a mobile state, while the forward movements of peri-nuclear microtubule tracks facilitate directional transport of the cargo during neuronal migration. I am now preparing manuscript for paper submission and the future experiment plans are as followed: (1) further characterization of Nesprin-2-dynein-dynactin-BicD2 binding through generating mutant molecules for biochemistry experiments, (2) intracellular cargo trafficking experiments with increased cargo size, (3) further characterization of microtubule sliding in migrating neurons.
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