Characterization of pathophysiological substrates of LRRK2, a causative gene product for familial Parkinson's disease

• Project/Area Number: 22790058
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: ITO Genta 東京大学, 大学院・医学系研究科, 助教 (10431892)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: パーキンソン病 / LRRK2 / キナーゼ / GTP結合蛋白質

Research Abstract

Several proteins have been reported to be phosphorylated by LRRK2 in vitro. However, they are not phosphorylated by LRRK2 in cells. In this study, we searched the database using the consensus phosphorylation sequence of LRRK2 as a query and selected a number of proteins as candidates. We examined whether they are phosphorylated by LRRK2 and found that several proteins including Synaptotagmin-1 were phosphorylated by LRRK2 in vitro.

Research Products

• [Journal Article] Re-examination of the dimerization state of leucine-rich repeat kinase 2 : predominance of the monomeric form (2012)
  • Author(s): Ito G, Iwatsubo T.
  • Journal Title: Biochemical Journal Volume: 441巻 Issue: 3 Pages: 987-994
  • DOI: 10.1042/bj20111215
  • Peer Reviewed
• [Journal Article] Phosphorylation of α-synuclein protein at Ser-129 reduces neuronal dysfunction by lowering its membrane binding property in Caenorhabditis elegans (2012)
  • Author(s): Kuwahara T, Tonegawa R, Ito G, Mitani S, Iwatsubo T
  • Journal Title: J. Biol. Chem. Volume: 287 Issue: 10 Pages: 7098-7109
  • DOI: 10.1074/jbc.m111.237131
  • Peer Reviewed
• [Presentation] Identification and functional characterization of novel autophosphorylation sites of LRRK2. (2011)
  • Author(s): 伊藤弦太,上川路翔悟,岩坪威
  • Organizer: 米国神経科学会
  • Place of Presentation: ワシントンDC、アメリカ合衆国
  • Year and Date: 2011-11-13
• [Presentation] Identification of in vivo autophosphorylation sites of LRRK2. (2011)
  • Author(s): 上川路翔悟,伊藤弦太,岩坪威
  • Organizer: 米国神経科学会
  • Place of Presentation: ワシントンDC、アメリカ合衆国
  • Year and Date: 2011-11-13
• [Presentation] Identification and functional characterization of novel autophosphorylation sites of LRRK2 (2011)
  • Author(s): Genta Ito
  • Organizer: Neuroscience 2011
  • Place of Presentation: Walter E.Washington Convention Center(アメリカ合衆国)
  • Year and Date: 2011-11-13
• [Presentation] Identification of in vivo autophosphorylation sites of LRRK2 (2011)
  • Author(s): Shogo Kamikawaji
  • Organizer: Neuroscience 2011
  • Place of Presentation: Walter E.Washington Convention Center(アメリカ合衆国)
  • Year and Date: 2011-11-13
• [Presentation] Biochemical characterization of the dimerization of LRRK2. (2010)
  • Author(s): 伊藤弦太,岩坪威
  • Organizer: 米国神経科学会
  • Place of Presentation: サンディエゴ、アメリカ合衆国
  • Year and Date: 2010-11-16
• [Presentation] Biochemical characterization of the dimerization of LRRK2 (2010)
  • Author(s): 伊藤弦太、岩坪威
  • Organizer: Neuroscience 2010
  • Place of Presentation: San Diego Convention Center(アメリカ合衆国)
  • Year and Date: 2010-11-16
• [Presentation] Rotenone treatment enhances apoptosis caused by G2019S familial Parkinson mutant LRRK2. (2010)
  • Author(s): 功刀隼人,伊藤弦太,岩坪威
  • Organizer: 米国神経科学会
  • Place of Presentation: サンディエゴ、アメリカ合衆国
  • Year and Date: 2010-11-14
• [Presentation] Rotenone treatment enhances apoptosis caused by G2019S familial Park inson mutant LRRK2 (2010)
  • Author(s): 功刀隼人、伊藤弦太、岩坪威
  • Organizer: Neuroscience 2010
  • Place of Presentation: San Diego Convention Center(アメリカ合衆国)
  • Year and Date: 2010-11-14
• [Presentation] 家族性パーキンソン病責任遺伝子産物LRRK2の新規基質探索 (2010)
  • Author(s): 新留一樹、伊藤弦太、岩坪威
  • Organizer: 日本認知症学会第29回学術集会
  • Place of Presentation: 愛知県産業労働センター、愛知県
  • Year and Date: 2010-11-05
• [Presentation] 家族性パーキンソン病責任遺伝子産物LRRK2の新規基質探索 (2010)
  • Author(s): 新留一樹、伊藤弦太、岩坪威
  • Organizer: 第29回日本認知症学会学術集会
  • Place of Presentation: ウインクあいち(愛知県名古屋市)
  • Year and Date: 2010-11-05
• [Remarks]
  • URL: http://web.f.u-tokyo.ac.jp/~neuropsc/entranceja2.html
• [Remarks]
  • URL: http://web.f.u-tokyo.ac.jp/~neuropsc/entranceja2.html