DISC1 regulates NRG1/ErbB signal pathway

• Project/Area Number: 25460284
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Nagoya University
• Principal Investigator: MORI DAISUKE 名古屋大学, 脳とこころの研究センター, 特任准教授 (00381997)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 統合失調症 / DISC1 / Neuregulin / 細胞内輸送 / ニューレグリン１ / プロセッシング / ニューレグリン / 国際情報交換 USA

Outline of Final Research Achievements

DISC1 is a candidate gene for susceptibility to schizophrenia. We have reported that DISC1 protein is accumulated on Golgi apparatus in cultured neurons, which suggests that it is a component of transporting vesicles budding from Trans-Golgi network. However, the functional significance of DISC1 on Golgi-apparatus has been essentially unknown. Here, we report that DISC1 interacts with intracellular domain of precursor pro-Neuregulin-1 (pro-NRG1) and regulates its secretion and then propose our hypothesis that DISC1 promotes the formation and budding of vesicles including DISC1-interacting proteins. For the more strict quantification of secretion, we developed a synchronized budding system of single-passed transmembrane protein through Golgi apparatus, and revealed that the budding of pro-NRG1 and the secretion of mature NRG1 were relatively impaired in full-length DISC1 deficient hippocampal neuron.

Research Products

• [Journal Article] Investigation of Rare Single-Nucleotide PCDH15 Variants in Schizophrenia and Autism Spectrum Disorders (2016)
  • Author(s): Ishizuka, K., H. Kimura, C. Wang, J. Xing, I. Kushima, Y. Arioka, T. Oya-Ito, Y. Uno, T. Okada, D. Mori, B. Aleksic, and N. Ozaki.
  • Journal Title: PLoS One Volume: 11 Issue: 4 Pages: e0153224-e0153224
  • DOI: 10.1371/journal.pone.0153224
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of resting state networks in patients with gliomas: connectivity changes in the unaffected side and its relation to cognitive function. (2015)
  • Author(s): Maesawa S, Bagarinao E, Fujii M, Futamura M, Motomura K, Watanabe H, Mori D, Sobue G, Wakabayashi T.
  • Journal Title: PLoS One Volume: 10 Issue: 2 Pages: e0118072-e0118072
  • DOI: 10.1371/journal.pone.0118072
  • Peer Reviewed / Open Access
• [Presentation] ニューレグリン-1前駆体の細胞内輸送機構 (2015)
  • Author(s): Daisuke Mori Keisuke Kuroda Daisuke Tsuboi, Akiko Kodama Norio Ozaki, Kozo Kaibuchi
  • Organizer: 日本神経科学大会
  • Place of Presentation: 兵庫県神戸市神戸国際会議場
  • Year and Date: 2015-07-30
• [Presentation] DISC1/Neuregulin-1と統合失調症 (2014)
  • Author(s): 森大輔
  • Organizer: 日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Regulation of pro-Neuregulin intracellular trafficking (2013)
  • Author(s): 森大輔
  • Organizer: 日本神経科学大会
  • Place of Presentation: 京都国際会議場（京都市）