Investigation of effect of GIGYF2 on signal transduction

• Project/Area Number: 21790856
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: 財団法人東京都医学研究機構 (2010); National Center of Neurology and Psychiatry (2009)
• Principal Investigator: HIGASHI Shinji 財団法人東京都医学研究機構, 東京都精神医学総合研究所, 研究員 (30365647)
• Co-Investigator(Renkei-kenkyūsha): ISEKI Eu 順天堂大学, 医学部, 教授 (30203061) ; MOORE Darren ローザンヌ工科大学, ブレインマインド研究所, 准教授
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 神経分子病態学 / パーキンソン病 / 神経変性 / GIGYF2 / インスリンシグナル / Grb10

Research Abstract

GIGYF2 has been reported as a candidate gene for PARK11-linked Parkinson's disease (PD). GIGYF2 was widely expressed, most highly in the pancreas and testis, and moderately in brain. GIGYF2 was present in Rab4-positive endosomes. Expression of GIGYF2 altered insulin-like growth factor-1 (IGF-1) receptor trafficking and enhanced IGF-1-induced ERK1/2 activation. We failed to find any differences in IGF-1-induced signaling between cells expressing wild-type and mutant GIGYF2 and observed only minimal expression of GIGYF2 in the nigrostriatal pathway, indicating no contribution of GIGYF2 to the pathogenesis of PD.

Research Products

• [Journal Article] Localization of MAP1-LC3 in vulnerable neurons and Lewy bodies brains patients with dementia bodies. (2011)
  • Author(s): Higashi S, Moore DJ, Minegishi M, Kasanuki K, Fujishiro H, Kabuta T, Togo Katsuse O, Uchikado Furukawa Y, Hino Kosaka Sato Arai Wada Iseki E.
  • Journal Title: Journal Neuropathology Experimental Neurology. 70巻 Pages: 264-280
  • Peer Reviewed
• [Journal Article] レビー小体型認知症と遺伝要因 (2011)
  • Author(s): 東晋二、井関栄三
  • Journal Title: 老年精神医学雑誌 22巻 Pages: 93-98
• [Journal Article] Localization of MAP1-LC3 in vulnerable neurons and Lewy bodies in brains of patients with dementia with Lewy bodies (2011)
  • Author(s): Shinji Higashi, 他
  • Journal Title: Journal of Neuropathology and Experimantal Neurology Volume: 70 Pages: 264-280
  • Peer Reviewed
• [Journal Article] レビー小体型認知症と遺伝要因 (2011)
  • Author(s): 東晋二, 他
  • Journal Title: 老年精神医学雑誌 Volume: 22 Pages: 93-98
• [Journal Article] TDP-43 physically interacts with Amyotrophic lateral sclerosis-linked mutant CuZn superoxide dismutase. (2010)
  • Author(s): Higashi S, Tsuchiya Y, Araki T, Wasa K,Kabuta T.
  • Journal Title: Neurochemistry international. 57巻 Pages: 906-913
  • Peer Reviewed
• [Journal Article] 妄想性障害と若年性認知症をどう診分けるか-レビー小体病を中心に- (2010)
  • Author(s): 東晋二、井関栄三
  • Journal Title: 精神科治療学 25巻 Pages: 1305-1309
• [Journal Article] GIGYF2 is present in endosomal compartments in the mammalian enhances compartments in the mammalian brains and enhances IGF-1-induced ERK1/2 activation. (2010)
  • Author(s): Higashi S, Iseki E,Minegishi M,Togo T, Kabuta T, Wada K.
  • Journal Title: Neurochemistry. 115巻 Pages: 423-437
  • Peer Reviewed
• [Journal Article] GIGYF2 is present in endosomal compartments in the mammalian brains and enhances IGF-1-induced ERK1/2 activation (2010)
  • Author(s): Shinji Higashi, 他
  • Journal Title: Journal of Neurochemistry Volume: 115 Pages: 423-437
  • Peer Reviewed
• [Journal Article] TDP-43 physically interacts with amyotrophic lateral sclerosis-linked mutant CuZn superoxide dimustase (2010)
  • Author(s): Shinji Higashi, 他
  • Journal Title: Neurochemistry International Volume: 57 Pages: 906-913
  • Peer Reviewed
• [Journal Article] 妄想性障害と若年性認知症をどう診分けるか-レビー小体病を中心に- (2010)
  • Author(s): 東晋二, 他
  • Journal Title: 精神科治療学 Volume: 25 Pages: 1305-1309
• [Journal Article] Abnormal localization of LRRK2 to the endosomal-lysosomal compartment in Lewy body disease. (2009)
  • Author(s): Higashi S, Moore DJ, Yamamoto R, Minegishi M, Sato K, Togo T, Katsuse O, Uchikado H,Furukawa Y, Hino H,Kosaka K, Emson PC, Wada K,Dawson VL, Dawson TM, Arai H, Iseki E.
  • Journal Title: Journal of Neuropathology and Experimental Neurology 68巻 Pages: 994-1005
  • Peer Reviewed
• [Journal Article] Abnormal localization of Leucine-Rich Repeat Kinase 2 to the Endosomal-Lysosomal Compartment in Lewy Body Disease (2009)
  • Author(s): Shinji Higashi, 他
  • Journal Title: Journal of Neuropathology and Experimantal Neurology 68 Pages: 994-1005
  • Peer Reviewed
• [Presentation] GIGYF2 is present in endosomal compartments in the mammalian brains and enhances IGF-1-induced ERK1/2 activation. (2010)
  • Author(s): Higashi s, et al.
  • Organizer: 14^th European Federation of Neurological Societies (EFNS) Congress.
  • Place of Presentation: スイスジュネーブPalexpo Congress Centre
  • Year and Date: 2010-09-26
• [Presentation] GIGYF2 is present in endosomal compartments in the mammalian brains and enhances IGF-1-induced ERK1/2 activation (2010)
  • Author(s): Shinji Higashi, 他
  • Organizer: 14^<th> European Federation of Neurological Societies (EFNS) Congress
  • Place of Presentation: Geneva, Switzerland
• [Presentation] レビー小体型認知症患者剖検脳におけるLRRK2のエンドソームコンパートメントへ局在 (2009)
  • Author(s): 東晋二, 他
  • Organizer: 第50回本神経病理学会
  • Place of Presentation: 香川県高松市サンポートホール高松・かがわ国際議場
  • Year and Date: 2009-06-06
• [Presentation] レビー小体型認知症患者剖検脳におけるLRRK2のエンドソームコンパートメントへの局在 (2009)
  • Author(s): 東晋二, 他
  • Organizer: 日本神経病理学会総会学術研究会
  • Place of Presentation: サンポートホール高松(香川県高松市)
  • Year and Date: 2009-06-06