Establishment of mitophagy imaging method

• Project/Area Number: 26860219
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Juntendo University
• Principal Investigator: Inoshita Tsuyoshi 順天堂大学, 医学(系)研究科(研究院), 助教 (20601206)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: パーキンソン病 / 神経科学 / シナプス小胞 / Vps35

Outline of Final Research Achievements

Neural function of Parkinson’s disease causative genes, PINK1 and Parkin were analyzed by using Drosophila model. Molecular genetical methods, immunostaining and live imaging showed that abnormal activity of Parkin affect accumulation of mitochondria in dopamine neurons. Neural activity were decreased by up-/down-regulation of Parkin activity and neural cell death were occurred. These results suggested that PINK1, Parkin mediated mitochondria clearance mechanisms is important for neural activity and viability.

Research Products

• [Journal Article] Vps35 in cooperation with LRRK2 regulates synaptic vesicle endocytosis through the endosomal pathway in Drosophila. (2017)
  • Author(s): 1.Tsuyoshi Inoshita , Taku Arano, Yuka Hosaka, Hongrui Meng, Yujiro Umezaki, Sakiko Kosugi, Takako Morimoto, Masato Koike, Hui-Yun Chang, Yuzuru Imai, Nobutaka Hattori
  • Journal Title: Human Molecular Genetics Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Regulation of vesicular trafficking by Parkinson’s disease-associated genes. (2015)
  • Author(s): Tsuyoshi Inoshita, Yuzuru Imai
  • Journal Title: AIMS Molecular Science Volume: 2 Issue: 4 Pages: 461-475
  • DOI: 10.3934/molsci.2015.4.461
  • Peer Reviewed
• [Journal Article] The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway. (2015)
  • Author(s): Imai Y, Kobayashi Y, Inoshita T, Meng H, Arano T, Uemura K, Asano T, Yoshimi K, Zhang CL, Matsumoto G, Ohtsuka T, Kageyama R, Kiyonari H, Shioi G, Nukina N, Hattori N, Takahashi R
  • Journal Title: PLoS Genet. Volume: 11 Issue: 9 Pages: e1005503-e1005503
  • DOI: 10.1371/journal.pgen.1005503
  • NAID: 120005946994
  • Peer Reviewed / Open Access
• [Journal Article] PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila. (2014)
  • Author(s): Shiba-Fukushima K, Inoshita T, Hattori N, Imai Y.
  • Journal Title: PLoS Genet. Volume: Jun 5;10(6) Issue: 6 Pages: 1004391-1004391
  • DOI: 10.1371/journal.pgen.1004391
  • Peer Reviewed / Open Access
• [Journal Article] Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering. (2014)
  • Author(s): Shiba-Fukushima K, Arano T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, Ryu KY, Nukina N, Hattori N, Imai Y.
  • Journal Title: PLoS Genet. Volume: 10 Issue: 12 Pages: 1004861-1004861
  • DOI: 10.1371/journal.pgen.1004861
  • Peer Reviewed / Open Access
• [Presentation] パーキンソン病原因遺伝子の一部は、シナプス小胞動態を制御する (2016)
  • Author(s): 井下 強、荒野 拓、穂坂 有加、孟 紅蕊、梅崎 勇次郎、小杉 紗紀子、森本 高子、小池 正人、Hui-Yun Chang、今居 譲、服部 信孝
  • Organizer: 第39回分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Synaptic vesicle dynamics are regulated by Parkinson’s disease-associated proteins Vps35 and LRRK2 (2016)
  • Author(s): Tsuyoshi Inoshita, Yuka Hosaka, Yuzuru Imai, Nobutaka Hattori
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 京都
• [Presentation] Synaptic vesicle dynamics are regulated by a subset of Parkinson’s disease genes. (2016)
  • Author(s): Tsuyoshi Inoshita, Changxu Cui, Yuzuru Imai、 Nobutaka Hattori
  • Organizer: 第３９回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Synaptic vesicle dynamics are regulated by a subset of Parkinson’s disease genes (2015)
  • Author(s): 井下 強
  • Organizer: 第３８回日本神経科学大会
  • Place of Presentation: 神戸・兵庫県
  • Year and Date: 2015-07-28
• [Presentation] Parkinson’s disease-associated proteins Vps35 and LRRK2 regulate synaptic release (2015)
  • Author(s): 井下 強
  • Organizer: 第５６回日本神経学会学術大会
  • Place of Presentation: 新潟・新潟県
  • Year and Date: 2015-05-20
• [Presentation] Parkinson’s disease-associated protein Vps35 regulates neuronal activities, which are modulated by Parkinson’s-disease associated protein kinase LRRK2 (2014)
  • Author(s): 井下 強
  • Organizer: 第３７回日本神経科学大会
  • Place of Presentation: 横浜市 パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] ドーパミン分泌の生体内ライブイメージング (2014)
  • Author(s): 井下 強
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡市 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24