| Project/Area Number |
16K07361
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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 | Center for Novel Science Initatives, National Institutes of Natural Sciences (2018)
Okazaki Research Facilities, National Institutes of Natural Sciences (2016-2017) |
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Principal Investigator |
Shiina Nobuyuki 大学共同利用機関法人自然科学研究機構(新分野創成センター、アストロバイオロジーセンター、生命創成探究, 生命創成探究センター, 准教授 (30332175)
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| Research Collaborator |
OHASHI Rie
KIMORI Yoshitaka
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | mRNA輸送 / 神経樹状突起 / RNA顆粒 / RNG105 / Arf / スパイン / AMPA受容体 / RNA granule / 局所的翻訳 / 神経 / シナプス / 学習・記憶 |
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| Outline of Final Research Achievements |
RNG105, a component of RNA granules responsible for mRNA transport and local translation in neuronal dendrites, is an RNA-binding protein essential for long-term memory formation. In this study, we focused on mRNAs identified as RNG105 target candidates (eight different mRNAs encoding GEFs and GAPs of small G protein Arf). mRNA imaging with an MS2-GFP tagging system in primary cultured neurons from mouse cerebral cortexes revealed that the Arf GEF and GAP mRNAs were localized to dendrites in an RNG105-dependent manner. Furthermore, knockdown of the Arf GEFs and GAPs in cultured neurons suggested that they are involved in synaptic strengthening by reducing immature types and increasing mature types of postsynapses (spines) on dendrites and by increasing the expression level of AMPA-type glutamate receptors on the cell surface of dendrites.
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| Academic Significance and Societal Importance of the Research Achievements |
神経樹状突起へのmRNA輸送および局所的翻訳は、シナプス強化や記憶に関与するが、数万種類存在するmRNAのうちどれがその責任を担うかは体系的に調べられていなかった。本研究は、長期記憶が顕著に低下するRNG105ノックアウトマウスの海馬において、樹状突起層への局在が低下したmRNAを網羅的に同定し、その中から遺伝子オントロジー解析によって「Arf制御因子mRNA群」を絞り込んだ。これらmRNA群が実際にRNG105依存的に樹状突起へ局在化し、シナプス強化に関与することを示した本研究は、長期記憶形成のメカニズムを理解する上で重要な因子及び制御機構を新たに提示した点で学術的意義が高い。
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