Regulation of dendritic spines by immediate-early gene product Arc

• Project/Area Number: 19500263
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: The University of Tokyo
• Principal Investigator: OKUNO Hiroyuki The University of Tokyo, 大学院・医学系研究科, 助教 (80272417)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 分子・細胞神経科学 / シナプス可塑性 / 脳・神経 / シグナル伝達 / シナプス / 遺伝子 / 長期記憶 / 海馬 / 活動依存的遺伝子発現 / 後シナプス肥厚部 / 前初期遺伝子 / 記憶

Research Abstract

神経特異的前初期遺伝子の産物であるArcは、長期シナプス可塑性および長期記憶形成に必須な分子である。本研究ではArcの発現制御機構およびシナプスにおける動態・機能制御機構を解析し、以下の成果を得た。1. Arc蛋白のスパイン局在はPSDタンパクとの相互作用によってシナプス活動依存的に制御されることが明らかになった。2. Arc遺伝子の神経活動依存的発現の分子機構を解明した。この応用して神経活動依存的な遺伝子発現レポーターを構築し、個体動物において脳活動の可視化に成功した。

Research Products

• [Journal Article] A synaptic activity-responsive element in the Arc/Arg3.1 promoter essential for synapse-to-nucleus signaling in activated neurons (2009)
  • Author(s): Kawashima T, Okuno H, Nonaka M, Adachi-Morishima A, Kyo N, Okamura M, Takemoto-Kimura S, Worley PF , Bito H.
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 316-321
  • Peer Reviewed
• [Journal Article] A synaptic activity-responsive element in the Arc/Arg3.1 promoter essential for synapse-to-nucleus signaling in activated neurons. (2009)
  • Author(s): Kawashima T, Okuno H, Nonaka M, Adachi-Morishima A, Kyo N, Okamura M, Takemoto-Kimura S, Worley PF and Bito H.
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 316-321
  • Peer Reviewed
• [Journal Article] シナプス機能とPSD構築を制御する分子機構 (2008)
  • Author(s): 尾藤晴彦、野中美応、布施俊光、藤井哉、竹本-木村さやか、奥野浩行
  • Journal Title: 蛋白質核酸酵素 53 Pages: 418-423
• [Journal Article] Regulation of dendritogenesis via a lipid-raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKl gamma (2007)
  • Author(s): Takemoto-Kimura S, Ageta-Ishihara N, Nonaka M, Adachi-Morishima A, Mano T, Okamura M, Fujii H, Fuse T, Hoshino M, Suzuki S, Kojima M, Mishina M, Okuno H, Bito H.
  • Journal Title: Neuron 54 Pages: 755-770
  • Peer Reviewed
• [Presentation] Synaptic activity-dependent regulation of neuronal immediate-early gene Arc/Arg3.1 (2008)
  • Author(s): Okuno H, Kawashima T, Adachi-Morishima A, Okamura M, Bito H
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会(BMB2008)
  • Place of Presentation: 神戸(口頭発表およびポスター)
  • Year and Date: 2008-12-10
• [Presentation] Critical genomic sequences for synaptic activity-dependent expression of the Arc gene (2008)
  • Author(s): Okuno H, Kawashima T, Adachi-Morishima A, Okamura M, Worley P, Bito H
  • Organizer: Soc. Neurosci. Abstr. 38.12, 第38回北米神経科学学会年会
  • Place of Presentation: Washington DC, USA. Poster
  • Year and Date: 2008-11-15
• [Presentation] Critical genomic sequences for synaptic activity-dependent expression of the Arc gene. (2008)
  • Author(s): Okuno, H., Kawashima, T., Adachi-Morishima, A., Okamura, M., Worley, P., Bito, H
  • Organizer: 38回北米神経科学学会年会
  • Place of Presentation: Washington DC, USA.
  • Year and Date: 2008-11-15
• [Presentation] 可塑性関連遺伝子Arcの活動依存的発現調節を担うゲノムエレメントの同定 (2008)
  • Author(s): 奥野浩行、川島尚之、安達-森島亜希、岡村理子、尾藤晴彦
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山(口頭発表)
  • Year and Date: 2008-09-13
• [Presentation] Regulation of synaptic localization of Arc protein through interaction with Ca2+/calmodulin-dependent kinase II beta (2008)
  • Author(s): Okuno H, Kawashima T, Nonaka M, Takemoto-Kimura S, Fujii H, Chowdhury S, Worley P, Bito H
  • Organizer: 6th FENS Forum 2008
  • Place of Presentation: Geneva, Switzerland, Poster
  • Year and Date: 2008-07-16
• [Presentation] Regulation of synaptic localization of Arc protein through interaction with Ca2+/calmodulin-dependent kinase II beta (2008)
  • Author(s): Okuno H., Kawashima T, Nonaka M., Takemoto-Kimura S, Fujii H., Chowdhury S., Worley P. F., Bito H.
  • Organizer: 6th FENS Forum
  • Place of Presentation: Geneva, Switzerland
  • Year and Date: 2008-07-16
• [Presentation] A novel synaptic activityresponsive element of the Arc promoter (2008)
  • Author(s): Kawashima T, Okuno H, Okamura M, Bito H
  • Organizer: 第31回日本神経科学大会(Neuroscience 2008)
  • Place of Presentation: 東京(口頭発表)
  • Year and Date: 2008-07-09
• [Presentation] Quantitative imaging for elucidating neuronal signal transduction mechanisms (2007)
  • Author(s): Okuno H, Fujii H, Nonaka M, Ageta-Ishihara N, Fuse T, Takemoto-Kimura S, Bito H
  • Organizer: 第30回日本分子生物年会・第80回日本生化学会大会・合同大会(BMB2007)
  • Place of Presentation: 横浜. Zeiss Lunchon symposium(口頭発表)
  • Year and Date: 2007-12-14
• [Presentation] Regulation of PSD complex by neuronal activity (2007)
  • Author(s): Okuno H, Fujii H, Fuse T, Nonaka M, Takemoto-Kimura S, Bito H
  • Organizer: 第30回日本分子生物年会・第80回日本生化学会大会・合同大会(BMB2007)
  • Place of Presentation: 横浜. Symposium
  • Year and Date: 2007-12-11
• [Presentation] Neonatal isolation induces susceptibility to learned helplessness through the decrease in LIMK1 in the adult rat hippocampus (2007)
  • Author(s): Morinobu S, Takahashi T, Iwamoto Y, Kawano K-I, Yamawaki S, Okuno H, Bito H
  • Organizer: Soc. Neurosci. Abstr. 501.2.第37回北米神経科学学会年会
  • Place of Presentation: San Diego, USA. Poster
  • Year and Date: 2007-11-05
• [Presentation] Synaptic targeting of Arc via high affinity interaction with Ca^<2+>/calmodulin-dependent kinase II beta (2007)
  • Author(s): Okuno H, Naruse H, Kawashima T, Fujii H, Nonaka M, Chowdhury S, Worley P, Bito H
  • Organizer: Soc. Neurosci. Abstr. 221.3, 第37回北米神経科学学会年会
  • Place of Presentation: San Diego, USA. Slide
  • Year and Date: 2007-11-04
• [Presentation] Synaptic targeting of Arc via high affinity interaction with Ca^<2+>/calmodulin-dependent kinase II beta. (2007)
  • Author(s): Okuno H, Naruse H, Kawashima T, Fuji H, Nonaka M, Chowdhury S., Worley P, Bito H
  • Organizer: 第37回北米神経科学学会年会
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2007-11-04
• [Presentation] Regulation of Arc localization at synapses via interaction with CaMKII beta (2007)
  • Author(s): Okuno H, Naruse H, Kawashima T, Fujii H, Chowdhury S, Worley P, Bito, H
  • Organizer: 第30回日本神経科学大会(Neuro2007)
  • Place of Presentation: 横浜(口頭発表)
  • Year and Date: 2007-09-10
• [Presentation] Regulation of Arc localization at synapses via interaction with CaMKII beta. (2007)
  • Author(s): OkunoH, Naruse H, Kawashima T, Fujii H, Chowdhury S, Worley P, Bito, H
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-10
• [Presentation] Regulation of Arc/Arg3.1localization in dendritic spines via interaction with Ca^<2+>/Calmodulin-dependent kinase II (2007)
  • Author(s): Okuno H, Fujii H, Naruse H, Kawashima T, Worley P, Bito H
  • Organizer: 7^<th> HFSP Awardee Meeting
  • Place of Presentation: Brisbane, Australia, Poster
  • Year and Date: 2007-07-19
• [Presentation] Regulation of Arc/Arg3.1 localization in dendritic spines via interaction with Ca^<2+>/Calmodulin-dependent kinase II. (2007)
  • Author(s): Okuno H, Fujii H, Naruse H, Kawashima T, Worley P, Bito H
  • Organizer: 7th HFSP Awardee Meeting
  • Place of Presentation: Brisbane, Australia
  • Year and Date: 2007-07-19
• [Presentation] Visualization of activity-dependent protein synthesis in dendritic regions of neurons (2007)
  • Author(s): Okuno H.
  • Organizer: 1st International Symposium on Nanomedicine-from Basic to Applications-(ISNM2007)/2nd Molecule-Based Information Transmission and Reception (MB-ITR2007)
  • Place of Presentation: Okazaki, Japan. Slide (invited)
  • Year and Date: 2007-04-21
• [Presentation] Optical analysis of activity-dependent protein synthesis in dendritic regions of neurons (2007)
  • Author(s): Okuno H, Naruse H, Bito H
  • Organizer: 2^<nd> International workshop on Approaches to Single-Cell Analysis
  • Place of Presentation: Tokyo, Japan. Poster
• [Book] 情報素子としてのシナプス-構造・機能ならびに新たな疾患制御標的としての意義-(ナノメディシン, 宇理須恒雄) (2008)
  • Author(s): 奥野浩行、藤井哉、尾藤晴彦
  • Publisher: オーム社、東京
• [Book] Activity-dependent gene regulation : How do synapses talk to the nucleus and fine-tune neuronal outputs(M. Zhuo)(Molecular Pain) (2008)
  • Author(s): Bito H, Takemoto-Kimura S, Okuno H.
  • Publisher: Molecular Pain(Springer)
• [Book] Activity-dependent gene regulation: How do synapsestalk to the nucleus and fine-tune neuronaloutputs?"Molecular Pain" (M.Zhuo, Ed) (2008)
  • Author(s): Bito H, Takemoto-Kimura S, Okuno H
  • Publisher: Springer
• [Book] 情報素子としてのシナプス-構造・機能ならびに新たな疾患制御標的としての意義-inナノメディシン宇理須恒雄 編 (2008)
  • Author(s): 奥野浩行、藤井哉、尾藤晴彦
  • Publisher: オーム社
• [Remarks] 2009年1月15日朝日新聞(近畿版)「記憶のきっかけDNA配列発見」雑誌掲載論文(Kawashima T, Okuno H,Nonaka M, Adachi-Morishima A, Kyo N,Okamura M, Takemoto-Kimura S, Worley Pfand Bito H. Proc. Natl. Acad. Sci. USA,106, 316-321, 2009.)に関しての研究内容紹介記事。
• [Remarks]
  • URL: http://www.neurochem.m.u-tokyo.ac.jp/
• [Remarks]
  • URL: http://www.neurochem.m.u-tokyo.ac.jp/