Molecular basis of neuron-specific, activity-dependent regulation of the plasticity-related gene Arc

• Project/Area Number: 21500301
• 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 東京大学, 大学院・医学系研究科, 助教 (80272417)
• Co-Investigator(Renkei-kenkyūsha): BITO Haruhiko 東京大学, 大学院・医学系研究科, 准教授 (00291964)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: シナプス / 脳・神経 / ゲノム / 転写調節 / Arc / シグナル伝達 / 遺伝子 / 長期記憶 / 海馬

Research Abstract

The neuronal immediate-early gene Arc, which plays critical roles in long-term synaptic plasticity and long-term memory formation, is dynamically regulated by neuronal activities in the brain. Through this study, we have determined several genomic regulatory elements in the Arc promoter, and have identified transcription factors that contribute to activity-dependent expression. We further uncovered a novel mechanism by which Arc protein is localized and thus regulates glutamate receptor trafficking at synapses.

Research Products

• [Journal Article] Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKllβ (2012)
  • Author(s): 奥野浩行, 他
  • Journal Title: Cell Volume: 149 Issue: 4 Pages: 886-898
  • DOI: 10.1016/j.cell.2012.02.062
  • Peer Reviewed
• [Journal Article] Schema-dependent gene activation and memory encoding in neocortex (2011)
  • Author(s): Tse, D ; Takeuchi, T ; Kakeyama, M ; Kajii, Y ; Okuno, H ; Tohyama, C ; Bito, H, Morris, RGM.
  • Journal Title: Science Volume: 333 Issue: 6044 Pages: 891-895
  • DOI: 10.1126/science.1205274
  • Peer Reviewed
• [Journal Article] Real-time measurements of protein dynamics using fluorescence activation-coupled protein labeling method (2011)
  • Author(s): Komatsu T, Johnsson K, Okuno H, Bito H, Inoue T, Nagano T, Urano Y
  • Journal Title: J. Am. Chem. Soc Volume: 133 Issue: 17 Pages: 6745-6751
  • DOI: 10.1021/ja200225m
  • Peer Reviewed
• [Journal Article] Regulation and function of immediate-early genes in the brain : beyond neuronal activity markers (2010)
  • Author(s): Okuno, H.
  • Journal Title: Neuroscience Res Volume: 69 Issue: 3 Pages: 175-186
  • DOI: 10.1016/j.neures.2010.12.007
  • Peer Reviewed
• [Journal Article] Synaptic Activity Responsive Element(SARE): a unique genomic structure with an unusual sensitivity to neuronal activity (2010)
  • Author(s): Inoue, M ; Yagishita-Kyo, N ; Nonaka, M ; Kawashima, T ; Okuno, H ; Bito, H.
  • Journal Title: Commun. Integr. Biol Volume: 3 Issue: 5 Pages: 443-446
  • DOI: 10.4161/cib.3.5.12287
  • Peer Reviewed
• [Journal Article] Synaptic tagging and capture : differential role of distinct calcium-calmodulin kinases in protein synthesis-dependent long-term potentiation (2010)
  • Author(s): Redondo, R. L ; Okuno, H ; Spooner, P. A ; Frenguelli, B. G ; Bito, H ; Morris, R. G. M.
  • Journal Title: J. Neurosci. Volume: 30 Issue: 14 Pages: 4981-4989
  • DOI: 10.1523/jneurosci.3140-09.2010
  • Peer Reviewed
• [Journal Article] シナプスから核へのシグナリングとシナプス活動依存的遺伝子発現:前初期遺伝子Arcの発現制御メカニズムを中心に (2010)
  • Author(s): 奥野浩行
  • Journal Title: 生化学 Volume: 82 Pages: 841-846
  • NAID: 10027502590
  • URL: http://wwwsoc.nii.ac.jp/jbiochem/magazine/82-09-07.pdf
  • Peer Reviewed
• [Journal Article] Regulation and function of immediate-early genes in the brain : be yond neuronal activity markers. (2010)
  • Author(s): Okuno H.
  • Journal Title: Neuroscience Res. Volume: 69 Pages: 175-186
  • Peer Reviewed
• [Journal Article] Synaptic Activity Responsive Element (SARE): a unique genomic structure with an unusual sensitivity to neuronal activity. (2010)
  • Author(s): Inoue M, Yagishita-Kyo N, Nonaka M, Kawashima T, Okuno H, Bito H.
  • Journal Title: Commun.Integr.Biol. Volume: 3 Pages: 443-446
• [Journal Article] Synaptic tagging and capture : differential role of distinct calcium/calmodulin kinases in protein synthesis-dependent long-term potentiation. (2010)
  • Author(s): Redondo RL, Okuno H, Spooner PA, Frenguelli BCC Bito H, Morris RGM.
  • Journal Title: J.Neurosci. Volume: 30 Pages: 4981-4989
  • Peer Reviewed
• [Journal Article] Synaptic tagging and capture : differential role of distinct calcium-calmodulin kinases in protein synthesis-dependent long-term potentiation. (2010)
  • Author(s): Redondo, R.L., Okuno, H., Spooner, P.A., Frenguelli, B.G., Bito, H., Morris, R.G.M
  • Journal Title: Journal of Neuroscience 30 Pages: 4981-4989
  • Peer Reviewed
• [Journal Article] シナプスから核へのシグナリング:シナプス可塑性を長期化する分子機構 (2009)
  • Author(s): 奥野浩行、川島尚之、野中美応、尾藤晴彦
  • Journal Title: 細胞工学 Volume: 28 Pages: 894-899
• [Journal Article] シナプスから核へのシグナリング:シナプス可塑性を長期化する分子機構 (2009)
  • Author(s): 奥野浩行、川島尚之、野中美応、尾藤晴彦
  • Journal Title: 細胞工学 28 Pages: 894-899
• [Presentation] Enhanced synaptic accumulation of activity-driven Arc protein during sensory deprivation in the mouse visual cortex (2011)
  • Author(s): Okuno, H ; Fujii, H ; Kawashima, T ; Nonaka, M ; Yagishita-Kyo, N ; Ishii, Y ; Takemoto-Kimura, S ; Chowdhury, S ; Worley, PF ; Bito, H.
  • Organizer: 第40回北米神経科学学会年会(Neuroscience 2010)
  • Place of Presentation: San Diegoコンベンションセンター(米国)
  • Year and Date: 2011-11-17
• [Presentation] Real-time imaging of synaptic receptor trafficking using a fluorescence activation-coupled protein labeling(FAPL) method (2011)
  • Author(s): Ishi, Y ; Okuno, H ; Tomatsu, T ; Nagano, T ; Urano, Y ; Bito, H.
  • Organizer: 第41回北米神経科学学会年会(Neuroscience 2011)
  • Place of Presentation: Washington DCコンベンションセンター(米国)
  • Year and Date: 2011-11-16
• [Presentation] Increased nuclear shuttling of CRTC1 enhances activity-regulated CREB-dependent gene expression and long-term memory formation (2011)
  • Author(s): Nonaka M ; Fukushima, H ; Kawashima, T ; Suzuki, K ; Okuno, H ; Kida, S ; Bito, H
  • Organizer: 第41回北米神経科学学会年会(Neuroscience 2011)
  • Place of Presentation: Washington DCコンベンションセンター(米国)
  • Year and Date: 2011-11-15
• [Presentation] Gene activation and memory encoding in neocortex during hippocampus-dependent learning (2011)
  • Author(s): Morris, RG.; Tse, D ; Takeuchi, T ; Kakeyama, M ; Kajii, Y ; Okuno, H ; Toyama, C ; Bito, H.
  • Organizer: 第41回北米神経科学学会年会(Neuroscience 2011)
  • Place of Presentation: Washington DCコンベンションセンター(米国)
  • Year and Date: 2011-11-14
• [Presentation] Mechanisms of Arc targeting to synapses (2011)
  • Author(s): Okuno, H.
  • Organizer: The 6th International Conference of Neurons and Brain Diseases/Association for the Study of Neurons and Diseases
  • Place of Presentation: 富山クラウンプラザホテル(富山県)
  • Year and Date: 2011-08-04
• [Presentation] Mechanisms of Arc targeting to synapses (2011)
  • Author(s): Okuno, H.
  • Organizer: The 6th International Conference of Neurons and Brain Diseases/Association for the Study of Neurons and Diseases
  • Place of Presentation: 富山クラウンプラザホテル (富山県富山市)(招待講演)
  • Year and Date: 2011-08-04
• [Presentation] Enhanced synaptic accumulation of activity-driven Arc protein during sensory deprivation in the mouse visual cortex. (2010)
  • Author(s): Okuno H, Fujii H, Kawashima T, Nonaka M, Yagishita-Kyo N, Ishii Y, Takemoto-Kimura S, Chowdhury S, Worley PF, Bito H.
  • Organizer: 北米神経科学学会年会(Neuroscience 2010)
  • Place of Presentation: San Diegoコンベンションセンター(米国)
  • Year and Date: 2010-11-17
• [Presentation] Dual FRET-based analysis of biochemical computation performed by neuronal Ca2+signaling processes (2010)
  • Author(s): Fujii, H ; Inoue, M ; Okuno, H ; Takemoto-Kimura, S ; Bito, H
  • Organizer: 第40回北米神経科学学会年会(Neuroscience 2010)
  • Place of Presentation: San Diegoコンベンションセンター(米国)
  • Year and Date: 2010-11-16
• [Presentation] Synaptic inactivity enhances postsynaptic contents of activity-induced Arc protein in the neocortex (2010)
  • Author(s): Okuno, H ; Kawashima, T ; Yagishita-Kyo, N ; Ishii, Y ; Takemoto-Kimura, S ; Bito, H.
  • Organizer: 第33回日本神経科学学会年会(Neuro2010)
  • Place of Presentation: 神戸コンベンションセンター(兵庫県)
  • Year and Date: 2010-09-04
• [Presentation] Synaptic inactivity enhances postsynaptic contents of activity-induced Arc protein in the neocortex. (2010)
  • Author(s): Okuno H, Kawashima T, Yagishita-Kyo N, Ishii Y, Takemoto-Kimura S, Bito H.
  • Organizer: 第33回日本神経科学学会年会(Neuro2010)
  • Place of Presentation: 神戸コンベンションセンター(兵庫県神戸市)
  • Year and Date: 2010-09-04
• [Presentation] Multiple regulatory elements in the Arc/Arg3. 1 promoter essential for synaptic activity-responsive gene expression in activated neurons (2009)
  • Author(s): Kawashima, K ; Okuno, H ; Bito, H.
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-12
• [Presentation] Multiple regulatory elements in the Arc/Arg3.1 promoter essential for synaptic activity-responsive gene expression in activated neurons. (2009)
  • Author(s): Kawashima, K., Okuno, H., Bito, H.
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2009-12-12
• [Presentation] Activity-dependent gene regulation and nucleus-to-synapse signaling for synaptic plasticity "UNAM Symposium" (2009)
  • Author(s): Okuno, H.
  • Organizer: Learning and Memory
  • Place of Presentation: UNAM神経生物学研究所(ケラタロ州・メキシコ)
  • Year and Date: 2009-11-12
• [Presentation] Activity-dependent gene regulation and nucleus-to-synapse signaling for synaptic plasticity (2009)
  • Author(s): Okuno, H.
  • Organizer: UNAM Symposium "Learning and Memory"
  • Place of Presentation: UNAM神経生物学研究所(ケラタロ州・メキシコ)
  • Year and Date: 2009-11-12
• [Presentation] Differential role of distinct calcium-calmodulin kinases in protein synthesis-dependent long-term potentiation (2009)
  • Author(s): Redondo, R. L ; Okuno, H ; Spooner, P. A ; Frenguelli, B. G ; Bito, H ; Morris, RG. M.
  • Organizer: 第39回北米神経科学学会年会(Neuroscience 2009)
  • Place of Presentation: Chicagoコンベンションセンター(米国)
  • Year and Date: 2009-10-18
• [Presentation] Single spine dual FRET imaging to better understanding synaptic biochemical network (2009)
  • Author(s): Fujii, H ; Inoue, M ; Ishii, Y ; Okuno, H ; Bito, H.
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2009-09-18
• [Presentation] Synaptic activity-dependent regulation of plasticity-related gene Arc/Arg3. 1. (2009)
  • Author(s): Okuno, H ; Kawashima, T ; Nonaka, M ; Nan, K ; Bito, H.
  • Organizer: IUPS2009
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2009-07-28
• [Presentation] Synaptic activity-dependent regulation of plasticity-related gene Arc/Arg3.1 (2009)
  • Author(s): Okuno, H., Kawashima, T., Mio, N., Nan, K., Bito, H
  • Organizer: IUPS2009
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 2009-07-28
• [Book] Encyclopedia of Signaling Molecules (2012)
  • Author(s): Yagishita-Kyo, N ; Inoue, M ; Nonaka, M ; Okuno, H ; Bito H.
  • Publisher: Springer(印刷中)
• [Book] "CREB" in "Encyclopedia of Signaling Molecules" (2012)
  • Author(s): Yagishita-Kyo N, Inoue M, Nonaka M, Okuno H, Bito H
  • Publisher: Springer(印刷中)
• [Book] CREB in "Encyclopedia of Signaling Molecules" (2011)
  • Author(s): Yagishita-Kyo N, Inoue M, Nonaka M, Okuno H, Bito H.
  • Publisher: Springer(掲載確定(印刷中))
• [Remarks] 本研究成果の一部は以下のURLで一般に公開されている。(1)東京大学Todai Research
  • URL: http://www.u-tokyo.ac.jp/ja/todai-research/research-information/the-law-of-the-synapses-punishing-the-weak-to-maintain-strong-synapses-strong/
• [Remarks] (2)科学技術振興機構プレスリリース
  • URL: http://www.jst.go.jp/pr/announce/20120511/index.html