Analysis of signal dynamics mediated by AMPK subfamily in synapse maturation

• Project/Area Number: 25640009
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: University of Yamanashi
• Principal Investigator: OHTSUKA Toshihisa 山梨大学, 総合研究部, 教授 (40401806)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 分子細胞神経科学 / アクティブゾーン / リン酸化 / シナプス / SAD / CAST / AMPK / 細胞極性 / 神経伝達物質

Outline of Final Research Achievements

Accumulating evidence suggests that serine /threonine kinase AMPK subfamily regulate neuronal polarization such as axon/dendrite formation. Here, we show that 1) MARK and AMPK1 are biochemically localized and expressed in the nerve terminals, in particular synaptic vesicles and active zone fractions; 2) phosphorylation of CAST regulates release of neurotransmitter from the active zone; and 3) SAD family may be involved in cell death. These results suggest that AMPK family member regulate not only neuronal polarization but also neurotransmitter release from the nerve terminals.

Research Products

• [Journal Article] The planar cell polarity protein Vangl2 bidirectionally regulates dendritic branching in cultured hippocampal neurons. (2014)
  • Author(s): Hagiwara, A., Yasumura, M., Hida, Y., Inoue, E., Ohtsuka, T.
  • Journal Title: Mol. Brain Volume: 7 Issue: 1 Pages: 79-79
  • DOI: 10.1186/s13041-014-0079-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CAST: functional scaffold for the integrity of the presynaptic active (2013)
  • Author(s): Ohtsuka, T.
  • Journal Title: Neurosci. Res. Volume: in press Issue: 1-2 Pages: 10-15
  • DOI: 10.1016/j.neures.2013.03.003
  • Peer Reviewed
• [Journal Article] Identification, expression and characterization of rat isoforms of the serum response factor (SRF) coactivator MKL1. (2013)
  • Author(s): Ishikawa, M., Shiota, J., Ishibashi, Y., Hakamata, T., Shoji, S., Fukuchi, M., Tsuda, M., Shirao, T., Sekino, Y., Ohtsuka, T., Baraban, J.M., Tabuchi, A.
  • Journal Title: FEBS Open Bio. Volume: 3 Issue: 1 Pages: 387-393
  • DOI: 10.1016/j.fob.2013.09.001
  • Peer Reviewed
• [Presentation] 神経終末アクティブゾーンの分子構造基盤とその破綻～プレシナプスから精神神経疾患の発症機構を捉える～ (2014)
  • Author(s): 大塚稔久
  • Organizer: 東京都医学総合研究所 招待講演
  • Place of Presentation: 東京都医学総合研究所(東京都）
  • Year and Date: 2014-08-15
  • Invited
• [Presentation] 神経終末アクティブゾーンの分子構造基盤と生理機能～分子から精神神経疾患の病態解明へ向けて～ (2014)
  • Author(s): 大塚稔久
  • Organizer: 北里大学医学会招待学術講演会
  • Place of Presentation: 北里大学（東京都）
  • Year and Date: 2014-07-31
  • Invited
• [Presentation] CAST and vesicle cycling at the ribbon synapses (2013)
  • Author(s): Toshihisa Ohtsuka
  • Organizer: Ribbon Synapses Symposium
  • Place of Presentation: Max-Planck-Institute for Experimental Medicine Goettingen, Germany
  • Invited
• [Presentation] CAST regulates the structure and function of presynaptic active zones (2013)
  • Author(s): 大塚稔久
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
• [Presentation] The presynaptic active zone molecular organization and physiological functions. (2013)
  • Author(s): 大塚稔久
  • Organizer: 神経構造生物学合同研究会
  • Place of Presentation: 生理学研究所（愛知県岡崎市）
• [Presentation] CAST Phosphorylation Mediates Short-term Synaptic Depression (2013)
  • Author(s): 大塚稔久
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館（京都府京都市）
• [Book] Presynaptic Terminals (2015)
  • Author(s): Ohtsuka, T.
  • Total Pages: 15
  • Publisher: Springer Japan
• [Remarks] 山梨大学医学部生化学講座第一教室
  • URL: http://www.med.yamanashi.ac.jp/basic/bioche01/
• [Remarks] 山梨大学医学部生化学講座第一教室
  • URL: http://www.med.yamanashi.ac.jp/basic/bioche01/