A novel mechanism to transmit information of extracellular signals to the cytoskeleton

• Project/Area Number: 24650174
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neuroscience in general
• Research Institution: National Institute for Basic Biology
• Principal Investigator: SHINTANI Takafumi 基礎生物学研究所, 統合神経生物学研究部門, 准教授 (10312208)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 細胞骨格 / APC2 / 細胞移動 / 神経細胞 / 脳 / 神経回路 / 情報伝達 / 神経組織 / 神経回路形成

Outline of Final Research Achievements

We analyzed Apc2-deficient mice, and found that a lack of Apc2 induces defective lamination in some brain regions, including the cerebral cortex, cerebellum, hippocampus, and olfactory bulb. APC2 is co-distributes with microtubules and actin fibers, and considered to be an essential mediator of the cytoskeletal regulation in response to extracellular signals. We further found that inhibition of APC2 functions on cytoskeleton by LRR is attenuated by a kinase inhibitor. We also generated LRR1- and LRR2-deficient mice.

Research Products

• [Journal Article] Loss of Function Mutation in APC2 Causes Sotos Syndrome Features. (2015)
  • Author(s): Almuriekhi, M., Shintani, T., Fahiminiya, S., Fujikawa, A., Kuboyama, K., Takeuchi, Y., Nawaz, Z., Nadaf, J., Kamel, H., Kitam, A.K., Samiha, Z., Mahmoud, L., Ben-Omran, T., Majewski, J. & Noda, M.
  • Journal Title: Cell Reports Volume: 10 Issue: 9 Pages: 1585-1598
  • DOI: 10.1016/j.celrep.2015.02.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The R3 receptor-like protein-tyrosine phosphatase subfamily inhibits insulin signaling by dephosphorylating the insulin receptor at specific sites. (2015)
  • Author(s): Shintani, T., Higashi, S., Takeuchi, Y., Gaudio, E., Trapasso, F., Fusco, A. & Noda, M.
  • Journal Title: Journal of Biochemistry Volume: -
  • NAID: 40020593541
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] SPIG1 negatively regulates BDNF maturation (2014)
  • Author(s): Suzuki R, Matsumoto M, Fujikawa A, Kato A, Kuboyama K, Yonehara K, Shintani T, Sakuta H, Noda M
  • Journal Title: J. Neurosci Volume: 34 Issue: 9 Pages: 3429-3442
  • DOI: 10.1523/jneurosci.1597-13.2014
  • Peer Reviewed
• [Journal Article] Substrate specificity of R3 receptor-like protein tyrosine phosphatase subfamily towards receptor protein tyrosine kinases (2013)
  • Author(s): Sakuraba J, Shintani T, Tani S, Noda M
  • Journal Title: J. Biol. Chem Volume: 288 Issue: 32 Pages: 23421-23431
  • DOI: 10.1074/jbc.m113.458489
  • Peer Reviewed
• [Journal Article] 脳の層構造を作る分子 (2013)
  • Author(s): 新谷隆史、野田昌晴
  • Journal Title: 化学と生物 Volume: 51 Pages: 655-656
• [Journal Article] Directional neuronal migration is impaired in mice lacking adenomatous polyposis coli 2. (2012)
  • Author(s): Shintani, et al.
  • Journal Title: Journal of Neuroscience Volume: 32(19) Issue: 19 Pages: 6468-84
  • DOI: 10.1523/jneurosci.0590-12.2012
  • Peer Reviewed
• [Presentation] SPIG1はBDNFのプロセッシングを負に制御する
  • Author(s): 鈴木亮子, 加藤彰, 米原圭祐, 藤川顕寛, 松本匡史, 新谷隆史, 作田拓, 野田昌晴
  • Organizer: 日本神経科学会
  • Place of Presentation: 京都国際会議場(京都府京都市)
• [Presentation] APC2は神経細胞の移動に必須である
  • Author(s): 新谷隆史、竹内靖、藤川顕寛、野田昌晴
  • Organizer: 日本神経科学大会
  • Place of Presentation: 名古屋国際会議場（愛知県）
• [Presentation] APC2欠損マウスにおいては神経細胞の指向的な移動に異常がある
  • Author(s): 新谷隆史、竹内靖、藤川顕寛、野田昌晴
  • Organizer: 福岡国際会議場
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Remarks] プレスリリース概要 脳の層構造を作る分子を発見
  • URL: http://www.nibb.ac.jp/pressroom/news/2012/05/09.html