Elucidation of APC2 functions in the regulation of cytoskeletal dynamics during neuronal development

• Project/Area Number: 23300126
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• 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): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 神経発生 / 神経分化 / 細胞骨格 / 細胞移動 / 神経回路 / 神経軸索 / 記憶・学習 / 情報伝達 / 神経組織 / 神経回路形成

Research Abstract

Adenomatous polyposis coli 2 (APC2) is mainly expressed in the nervous system and known to regulate microtubule stability in neurons. I show that a lack of Apc2 induces severe laminary defects in some regions of the brain including the cerebral cortex and cerebellum. In vivo BrdU labeling and immunohistochemical analyses with specific markers suggested that the laminary abnormalities are a result of poorly regulated neuronal migration by a cell-autonomous mechanism. Analyses of cerebellar granule cells revealed that the BDNF-stimulated directional migration is impaired in Apc2-deficient cells. We found that APC2 is distributed along actin fibers as well as microtubules by TIRF microscopy, and that BDNF-stimulated F-actin formation at the leading edge is impaired in Apc2-deficient neurons due to the dysregulation of Rho GTPase activity. These results suggest that APC2 is an essential mediator of the cytoskeletal regulation at leading edges in response to extracellular signals.

Research Products

• [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] 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(10) Pages: 665-666
  • URL: http://www.jsbba.or.jp/pub/journal_kasei/kasei_contents/vol51_10_2013.html
• [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: 665-666
• [Journal Article] A distinct effect of transient and sustained upregulation of cellular factor XIII in the goldfish retina and optic nerve on optic nerve regeneration. (2012)
  • Author(s): Sugitani, et al.
  • Journal Title: Neurochemistry International Volume: 61(3) Issue: 3 Pages: 423-32
  • DOI: 10.1016/j.neuint.2012.06.004
  • Peer Reviewed
• [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 (2013)
  • 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: 第36回日本神経科学会大会
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 2013-06-21
• [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 (2012)
  • Author(s): 新谷隆史, 竹内靖, 藤川顕寛, 野田昌晴
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 2012-12-12
• [Presentation] APC2は神経細胞の移動に必須である (2012)
  • 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(名古屋)
  • Year and Date: 2012-09-20
• [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: 日本神経科学大会
  • 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(愛知県名古屋市)
• [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: 日本分子生物学会
  • Place of Presentation: 福岡国際会議場(福岡県福岡市)
• [Remarks]
  • URL: http://niwww3.nibb.ac.jp/