The mechanism that regulates CREB activator to repressor ratio in Drosophila.

• Project/Area Number: 25430030
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: MIYASHITA Tomoyuki 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 主席研究員 (70270668)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: CREB / alternative splicing / K-homology(KH) domain / K-hmology protein

Outline of Final Research Achievements

CREB-dependent gene expression is critical for long-term memory (LTM) formation. In Drosophila single CREB (dCREB2) gene generates both activator dCREB2a and 2d and repressor dCREB2b isoforms by alternative splicing. Thus, it has been suggested that activator to repressor (activator/repressor) ratio is critical for LTM-related gene expression and this ratio is increased by spaced training which produces LTM. However, the splicing mechanism that regulates activator/repressor ratio is not yet known.
To explore the mechanism that regulates activator/repressor ratio, we focused on K-homology(KH) domain proteins which regulates alternative splicing of mRNA. In this study we report a KH domain protein which expression was increased by overexpressing dCREB2d, during spaced training. We suspect that this KH domain protein may play critical role in activator/repressor regulation during LTM formation.

Research Products

• [Journal Article] Long-Term Memory Formation in Drosophila Requires Training-Dependent Glial Transcription (2015)
  • Author(s): Matsuno M, Horiuchi J, Yuasa Y, Ofusa K, Miyashita T, Masuda T, and Saitoe M
  • Journal Title: The Journal of Neuroscience Volume: 35 Issue: 14 Pages: 5557-5565
  • DOI: 10.1523/jneurosci.3865-14.2015
  • Peer Reviewed / Open Access
• [Journal Article] Glial dysfunction causes age-related memory impairment in Drosophila. (2014)
  • Author(s): Yamazaki D, Horiuchi J, Ueno K, Ueno T, Saeki S, Matsuno M, Naganos S, Miyashita T, Hirano Y, Nishikawa H, Taoka M, Yamauchi Y, Isobe T, Honda Y, Kodama T, Masuda T, Saitoe M
  • Journal Title: Neuron Volume: 84 Issue: 4 Pages: 753-763
  • DOI: 10.1016/j.neuron.2014.09.039
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Spaced training時に形成されるc-fos / CREB transcription cycle (2014)
  • Author(s): 宮下知之、齊藤実
  • Organizer: 第37回 日本神経科学会大会
  • Place of Presentation: パシフィコ横浜（神奈川県 横浜）
  • Year and Date: 2014-09-12
• [Remarks] 東京都医学研 学習記憶プロジェクト
  • URL: http://www.igakuken.or.jp/memory/