Molecular mechanisms of neurite self-avoidance
| Project/Area Number |
18K06207
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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 44010:Cell biology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Kise Yoshiaki 東京大学, 大学院理学系研究科(理学部), 特任准教授 (70769611)
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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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 樹状突起 / 軸索 / イオンチャネル / 自己交叉忌避 / シグナル伝達 |
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| Outline of Final Research Achievements |
This project aims to reveal the molecular mechanisms of neuronal development, maintenance, and function in the brain. To this end, we first identified the regulators of cytoskeleton which work downstream of cell-recognition molecule Dscam for dendrite self-avoidance. Second, we identified Wnk kinase which is required for the growth/branching as well as maintenance of axon. Finally, we provided, by using cryo-EM, the structural basis for gating modulation of Kv4.2-KChIP1-DPP6S channel complex which is required for the inhibition of the backpropagation of the action potential in dendrites.
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| Academic Significance and Societal Importance of the Research Achievements |
我々ヒトの脳神経系は、1000億個もの神経細胞がその複雑な分枝パターンをもった樹状突起と軸索を介して精密なネットワークを形成し、情報処理、運動、学習、意思決定などを行う。本研究成果の学術的な意義は、（１）樹状突起や軸索の分枝パターン形成と維持の機構を明らかしたこと、（２）神経細胞が機能的電気信号を生み出すために必須なカリウムチャネルの活性制御機構を明らかにしたことによって、神経細胞の発生と機能の両面のメカニズムに迫ることができた点である。その社会的意義は、損傷を受けた脳の再生や、イオンチャネルの機能不全による精神疾患の治療という医療への応用にも道を切り開いたことである。
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Report
(5 results)
Research Products
(13 results)
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[Journal Article] Axon morphogenesis and maintenance require an evolutionary conserved safeguard function of Wnk kinases antagonizing Sarm and Axed2021
Author(s)
Izadifar A, Courchet J, Virga DM, Verreet T, Hamilton S, Ayaz D, Misbaer A, Vandenbogaerde S, Monteiro L, Petrovic M, Sachse S, Yan B, Erfurth ML, Dascenco D, Kise Y, Yan J, Edwards-Faret G, Lewis T, Polleux F, Schmucker D.
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Journal Title
Neuron
Volume: 109
Issue: 18
Pages: 2864-2883
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation.2019
Author(s)
Sachse SM, Lievens S, Ribeiro LF, Dascenco D, Masschaele D, Horre K, Misbaer A, Vanderroost N, De Smet AS, Salta E, Erfurth ML, Kise Y, Nebel S, Van Delm W, Plaisance S, Tavernier J, De Strooper B, De Wit J, Schmucker D.
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Journal Title
EMBO J
Volume: 38
Issue: 6
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Wnk regulates Nmnat and Axundead during axon morphogenesis and maintenance2019
Author(s)
Izadifar A., Courchet J., Verreet T., Ayaz D., Petrovic M., Sachse S. Misbaer A., Vandenbogaerde S., Yan B., Erfurth ML, Dascenco D., Kise Y., Yan J., Lewis T., Polleux F., Schmucker D.
Organizer
3rd Axon Meeting "Circuits Development & Axon Regeneration" at Spain
Related Report
Int'l Joint Research
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