Analyses of factors acting with Parkinson's disease gene LRRK2 using nematode as a model organism

• Project/Area Number: 23590331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: HISAMOTO Naoki 名古屋大学, 理学(系)研究科(研究院), 准教授 (80283456)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 細胞内シグナル伝達 / LRRK2 / C. elegans / パーキンソン病 / C.エレガンス / LRK-1 / Cエレガンス

Research Abstract

It is known that mutations in LRRK2 are linked to both sporadic and familial Parkinson's disease in human. We identified two human proteins that bind to LRRK2: BAG-2 and HSC70, which are known to form a chaperone complex. In addition, we characterized that their C. elegans homologs, UNC-23 and HSP-1, regulate polarized sorting of synaptic vesicle proteins by determining Golgi localization of LRK-1, the sole homolog of human LRRK. Furthermore, we demonstrated that LRK-1 acts with p38 MAP kinase pathway to protect C. elegans dopaminergic neurons from 6-OHDA toxicity.

Research Products

• [Journal Article] Forgetting in C. elegans is accelerated by neuronal communication via the TIR-1/JNK-1 pathway. (2013)
  • Author(s): Inoue A, Sawatari E, Hisamoto N, Kitazono T, Teramoto T, Fujiwara M, Matsumoto K, Ishihara T.
  • Journal Title: Cell Reports Volume: 3(3) Issue: 3 Pages: 808-819
  • DOI: 10.1016/j.celrep.2013.02.019
  • Peer Reviewed
• [Journal Article] The C. elegans JNK signaling pathway activates expression of stress response genes by derepressing the Fos/HDAC repressor complex (2013)
  • Author(s): Ayuna Hattori
  • Journal Title: PLOS Genetics Volume: 9 Issue: 2 Pages: e1003315-e1003315
  • DOI: 10.1371/journal.pgen.1003315
  • Peer Reviewed
• [Journal Article] 軸索再生とMAPキナーゼ (2013)
  • Author(s): 久本直毅、松本邦弘
  • Journal Title: Clinical Neuroscience Volume: 31 Pages: 667-668
• [Journal Article] Endocannabinoid-Goα signalling inhibits axon regeneration in Caenorhabditis elegans by antagonizing Gqα-PKC-JNK signalling. (2012)
  • Author(s): Pastuhov et al.
  • Journal Title: Nature Communications Volume: 3 Issue: 1 Pages: 1136-1136
  • DOI: 10.1038/ncomms2136
  • Peer Reviewed
• [Journal Article] The growth factor SVH-1 regulates axon regeneration in C.elegans via the JNK MAPK cascade (2012)
  • Author(s): Chun Li
  • Journal Title: Nature Neuroscience Volume: 15 Issue: 4 Pages: 551-557
  • DOI: 10.1038/nn.3052
  • Peer Reviewed
• [Journal Article] Axon regeneration requires coordinate activation of p38 and JNK MAPK pathways (2011)
  • Author(s): Nix, P., Hisamoto, H., Matsumoto, K., and Bastiani, M
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108 Issue: 26 Pages: 10738-10743
  • DOI: 10.1073/pnas.1104830108
  • Peer Reviewed
• [Journal Article] Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans (2011)
  • Author(s): Yuan, Y., Cao, P., Smith, M. A., Kramp, K., Huang, Y., Hisamoto, N., Matsumoto, K., Hatzoglou, M., Jin, H., and Feng, Z
  • Journal Title: PLoS One Volume: 6 Issue: 8 Pages: e22354-e22354
  • DOI: 10.1371/journal.pone.0022354
  • Peer Reviewed
• [Journal Article] Regulation of anoxic death in Caenorhabditis elegans by mammalian apoptosis signal-regulating kinase (ASK) family proteins (2011)
  • Author(s): Hayakawa, T., Kato, K., Hayakawa, R., Hisamoto, N., Matsumoto, K., Takeda, K. and Ichijo, H.
  • Journal Title: Genetics Volume: 187 Issue: 3 Pages: 785-792
  • DOI: 10.1534/genetics.110.124883
  • Peer Reviewed
• [Journal Article] The C. elegans JIP3 protein UNC-16 functions as an adaptor to link kinesin-1 with cytoplasmic dynein (2011)
  • Author(s): Arimoto, M., Koushika, S. P., Choudhary, B. C., Li, C., Matsumoto, K., and Hisamoto, N
  • Journal Title: J. Neurosci Volume: 31 Issue: 6 Pages: 2216-2224
  • DOI: 10.1523/jneurosci.2653-10.2011
  • Peer Reviewed
• [Presentation] The C. elegans plasminogen/HGF-like protein SVH-1 is required for larval developmental growth. (2013)
  • Author(s): Naoki Hisamoto
  • Organizer: 19th International C.elegans meeting
  • Place of Presentation: Los Angeles, USA
• [Presentation] (2012)
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋(口頭発表)
• [Presentation] Regulation of axon regeneration via a JNK pathway in C. elegans. (2012)
  • Author(s): 久本直毅
  • Organizer: 日本神経科学学会
  • Place of Presentation: 名古屋国際会議場 (愛知県)
• [Presentation] (2011)
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Invited
• [Presentation] MAPキナーゼホスファターゼによる神経軸索再生制御 (2011)
  • Author(s): 久本直毅
  • Organizer: 日本生化学会(招待講演)
  • Place of Presentation: 京都国際会館