| Project/Area Number |
18K06235
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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 | Institute of Physical and Chemical Research |
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Principal Investigator |
Kimura Makoto 国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (00290891)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 核輸送 / importin / 細胞分化 / 核-細胞質間蛋白質輸送 |
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| Outline of Final Research Achievements |
The expression levels of the importinα/β family nucleocytoplasmic transport receptors were analyzed by immunoblotting in several types of culture cells that can be inducibly differentiated. The expression levels altered remarkably in the monocyte-derived THP-1 cells during the differentiation into macrophage-like cells. Mass spectrometry-based quantitative proteomics was performed on the total and nuclear protein extracted before and after the differentiation. Proteins involved in protein degradation were increased in the nuclei of the differentiated cells, whereas those participating in DNA synthesis or chromosome organization decreased, consistent with the nature of this differentiation. Similar quantitative proteomics was done on the THP-1 cells with siRNA knock-down of the importinα5, which increases markedly during the differentiation, and candidate cargoes that may be transported by the importinβ/α5 heterodimer during the differentiation were identified.
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| Academic Significance and Societal Importance of the Research Achievements |
核輸送の研究分野では、importinα/βファミリー輸送因子の発現特異性の観察例と輸送因子特異的基質の同定数の著しい増加を受け、核輸送システムの構成変化を介した核内蛋白質成分の調節による細胞制御機構の重要性が認識され始めた。本研究は、特定の細胞分化過程での輸送因子の発現変動解析と核蛋白質のプロテオミクス解析を合わせて行い、また、その核蛋白質成分変化への一つの輸送因子の寄与を解析した点に新規性をもち、今後発展が予想される輸送調節による細胞制御機構の網羅的解析の先行例となることが期待される。
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