Examination of involvement of vesicle transport mechanism in neurodegenerative disease using tissue specific gene deletion method
| Project/Area Number |
16K07296
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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 |
Functional biochemistry
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| Research Institution | Nara Women's University |
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Principal Investigator |
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 小胞輸送 / ARF / 神経特異的欠損 / 細胞増殖遅延 / BMPシグナル亢進 / 小胞輸送機構 / Arf1 / Arf6 / 神経異常 / SMAP1 / SMAP2 / 神経変性疾患 / 膜輸送と輸送タンパク質 / 低分子量Gタンパク質 / 運動機能障害 |
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| Outline of Final Research Achievements |
A mouse lacking Arf1 only in neurons dies shortly after weaning with movement disorder of the hind limbs. We clarified the decrease in the number of granule cells in the cerebellum. We succeeded in creating a Fucci-expressing cell line capable of analyzing the doubling time and cell cycle in Arf1-deficient MEF cells. When tissue-specific deletion of Arf 1 and/or 6 in T and B lymphocytes were induced, abnormalities in the immune mechanism (such as abnormal maturation and abnormal antibody secretion) were found. We succeeded in generating mice for the preparation of Arf1 & 6 double-deficient MEF cells. In the SMAP1 & 2 double-deficient cells, we found that the signal loss is specifically delayed in the activity of the BMP signal (duration of the activity).
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果によって、「神経変性疾患を小胞輸送異常が引き起こす疾患」として捉えすことの妥当性が、小胞形成開始因子として細胞で良く解析されてきたArf1を用いてマウス個体レベルで示されたことは学術的に大きな意義がある。逆を考えれば、Arf1の活性化薬剤は神経変性疾患の予防や治療に応用できるかもしれないという社会的な意義も求められる。さらに、免疫をつかさどるT細胞、B細胞でのArf1の重要性を発見したことは、免疫系における新しいArf1機能の解明を期待させ、学術的にも社会的にも意義がある。
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] BRCA1-interacting protein OLA1 requires interaction with BARD1 to regulate centrosome number.2018
Author(s)
Yoshino Y, Qi H, Fujita H, Shirota M, Abe S, Komiyama Y, Shindo K, Nakayama M, Matsuzawa A, Kobayashi A, Ogoh H, Watanabe T, Ishioka C and Chiba N.
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Journal Title
Molecular Cancer Research
Volume: 6(10)
Pages: 1499-1511
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth.2018
Author(s)
M Morita, T Sato, M Nomura, Y Sakamoto, Y Inoue, R Tanaka, S Ito, K Kurosawa, K Yamaguchi, Y Sugiura, H Takizaki, Y Yamashita, R Katakura, I Sato, Y Okada, H Watanabe, G Kondoh, et al.
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Journal Title
Cancer Cell
Volume: 12
Pages: 355-367
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mllt10 knockout mouse model reveals critical role of Af10-dependent H3K79 methylation in midfacial development2017
Author(s)
2.Honami Ogoh, Kazutsune Yamagata, Tomomi Nakao, Lisa L. Sandell, Ayaka Yamamoto, Aiko Yamashita, Naomi Tanga, Mai Suzuki, Takaya Abe, Issay Kitabayashi, Toshio Watanabe, Daisuke Sakai
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Journal Title
Scientific Reports
Volume: 7
Pages: 11922-11922
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Af10 regulates mid facial development via H3K79 methylation2018
Author(s)
Honami Ogoh, Kazutsune Yamagata, Tomomi Nakao, Lisa L. Sandell, Issay Kitabayashi, Toshio Watanabe and Daisuke Sakai
Organizer
Gordon Research Seminar &Conference "Craniofacial Morphogenesis & Tissue Regeneration" Understanding Mechanisms of Craniofacial Development, Disease and Regeneration.
Related Report
Int'l Joint Research
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