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

2013 Fiscal Year Final Research Report

• 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
• Keywords: 細胞内シグナル伝達

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 Pages: 808-816
  • DOI: 10.1016/j.celrep.2013.02.019
• [Journal Article] The C. elegans JNK signaling pathway activates expression of stress response genes by derepressing the Fos/HDAC repressor complex (2013)
  • Author(s): Hattori A, Mizuno T, Akamatsu M, Hisamoto N, Matsumoto K
  • Journal Title: PLoS Genetics Volume: 9 Pages: e1003315
  • DOI: 10.1371/journal.pgen.1003315
• [Journal Article] Endocannabinoid-Goαsignalling inhibits axon regeneration in Caenorhabditis elegans by antagonizing the Gqα-PKC-JNK signalling (2012)
  • Author(s): Pastuhov SI, Fujiki K, Nix P, Kanao S, Bastiani M, Matsumoto K, Hisamoto N
  • Journal Title: Nature Commun Volume: 3 Pages: 1136
  • DOI: 10.1038/ncomms2136
• [Journal Article] The growth factor SVH-1 regulates axon regeneration in C. elegans via the JNK MAPK cascade (2012)
  • Author(s): Li C, Hisamoto N, Nix P, Kanao S, Mizuno T, Bastiani M, Matsumoto K
  • Journal Title: Nature Neurosci Volume: 15 Pages: 551-557
  • DOI: 10.1038/nn.3052
• [Journal Article] Axon regeneration requires coordinate activation of p38 and JNK MAPK pathways (2011)
  • Author(s): Nix P, Hisamoto N, Matsumoto K and Bastiani M
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108 Pages: 10738-10743
  • DOI: 10.1073/pnas.1104830108
• [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 MA, Kramp K, Huang Y, Hisamoto N, Matsumoto K, Hatzoglou M, Jin H, Feng Z
  • Journal Title: PLoS One Volume: 6 Pages: e22354
  • DOI: 10.1371/journal.pone.0022354
• [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, Ichijo H
  • Journal Title: Genetics Volume: 187 Pages: 785-792
  • DOI: 10.1534/genetics.110.124883
• [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 SP, Choudhary B, Li C, Matsumoto K, Hisamoto N
  • Journal Title: J. Neurosci Volume: 31 Pages: 2216-2224
  • DOI: 10.1523/JNEUROSCI.2653-10.2011
• [Presentation] (2012)
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋(口頭発表)
  • Year and Date: 20120918-21
• [Presentation] (2011)
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 20110921-24
  • Invited