Functional analysis of DISC1 using Disc1-knockout mouse

• Project/Area Number: 24700377
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Nagoya University
• Principal Investigator: TSUBOI Daisuke 名古屋大学, 医学(系)研究科(研究院), 特任助教 (80584672)
• Co-Investigator(Renkei-kenkyūsha): KAIBUCHI Kozo 名古屋大学, 大学院医学系研究科, 教授 (00169377)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 統合失調症 / 神経科学 / シナプス可塑性

Outline of Final Research Achievements

Schizophrenia is a devastating psychiatric disorder affecting 1% of the population worldwide. The DISC1 gene locus was originally identified at the breakpoint of a balanced (1;11) (q42;q14) chromosome translocation that co-segregates with schizophrenia, bipolar disorder, and recurrent major depression in a large Scottish family. Therefore, DISC1 gene is a promising susceptibility factor for schizophrenia. In the present study, using a proteomic analysis, I identified RNA-binding proteins including HZF as novel DISC1-interactors. HZF is a component of the RNA granules with inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) mRNA, which acts as a key regulator for synaptic plasticity. DISC1 co-localized with HZF and ITPR1 mRNA in hippocampal dendrites. Furthermore, DISC1 directly associated with several mRNAs including that of ITPR1. The impairment of DISC1 function prohibited the dendritic transport of ITPR1 mRNA and caused altered synaptic plasticity

Research Products

• [Journal Article] Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity. (2015)
  • Author(s): Tsuboi D, Kuroda K, Tanaka M, Namba T, Iizuka Y, Taya S, Shinoda T, Hikita T, Muraoka S, Iizuka M, Nimura A, Mizoguchi A, Shiina N, Sokabe M, Okano H, Mikoshiba K, Kaibuchi K
  • Journal Title: Nature Neuroscience Volume: in press Issue: 5 Pages: 698-707
  • DOI: 10.1038/nn.3984
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of rare, single-nucleotide mutations in NDE1 and their contributions to schizophrenia susceptibility (2015)
  • Author(s): Kimura H, Tsuboi D, Wang C, Kushima I, Koide T, Ikeda M, Iwayama Y, Toyota T, Yamamoto N, Kunimoto S, Nakamura Y, Yoshimi A, Banno M, Xing J, Takasaki Y, Yoshida M, Aleksic B, Uno Y, Okada T, Iidaka T, Inada T, Suzuki M, Ujike H, Kunugi H, Kato T, Yoshikawa T, Iwata N, Kaibuchi K
  • Journal Title: Schizophrenia Bulltein Volume: 41 Issue: 3 Pages: 744
  • DOI: 10.1093/schbul/sbu147
  • URL: https://pure.teikyo.jp/en/publications/76550df3-d250-41f7-bda1-72fe448db1dd
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 海馬神経細胞においてDISC1はIP3受容体mRNAの輸送を制御する (2013)
  • Author(s): 坪井大輔
  • Organizer: 第３６回日本神経科学大会
  • Place of Presentation: 国立京都国際会館（京都市）
• [Presentation] Patho-physiological functions of DISC1, a susceptibility gene of schizophrenia (2013)
  • Author(s): 坪井大輔
  • Organizer: The 2nd Brain Deseases and Molecular Machines Conference
  • Place of Presentation: フランス大使館（東京都港区）
  • Invited
• [Presentation] プロテオミクスから見た統合失調症の病態生理 (2012)
  • Author(s): 坪井大輔
  • Organizer: 第１０回日本プロテオーム学会
  • Place of Presentation: 日本科学未来館、東京
  • Invited
• [Presentation] Disrupted-In-Schizoprenia-1 regulates transport of neuronal mRNA. (2012)
  • Author(s): Tsuboi, D., Kuroda, K., Iizuka, Y., Okano, H., Mikoshiba, K., and Kaibuchi, K
  • Organizer: The 42nd Annual Meeting the Society for Neuroscience Society
  • Place of Presentation: ニューオリンズ、アメリカ
• [Book] 実験医学2015年6月号 (2015)
  • Author(s): 坪井大輔、森大輔、永井拓、山田清文、尾崎紀夫、貝淵弘三
  • Publisher: 羊土社