Expression and synaptic targeting of the neuronal immediate-early gene Arc

• Project/Area Number: 17500201
• 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 University of Tokyo, Graduate School of Medicine, Research Associate, 大学院医学系研究科, 助手 (80272417)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Arc / Activity-dependent gene expression / Synaptic plasticity / Spines / postsynaptic densities / 後シナプス肥厚部

Research Abstract

The neuronal immediate early gene Arc is dynamically regulated by synaptic activity and tightly linked to information processing in neuronal circuits. Recent studies have indicated that Arc plays roles in synaptic plasticity/homeostasis and long-term memory formation. However, molecular mechanisms of Arc functions at the synapse have still remained unclear. We therefore investigated 1) interaction between Arc and postsynaptic protein, 2) activity-dependent targeting of Arc into synapses, and 3) activity-dependent regulation of Arc expression. As results, we have obtained following findings.
1) Arc interacted with proteins in the endocytic machinery, and regulated glutamate receptors at the synapse (Chowdhury et al., Neuron, 52, p445-459, 2007).
2) Synaptic targeting of Arc was dynamically regulated by neuronal activity. Protein-protein interaction was likely involved in this process (Okuno et al., submitted).
3) Several regulatory elements that were critical for activity-dependent, neuron-specific expression, were characterized in the Arc promoter.
4) Interaction between Arc and an Arc-binding protein was visualized in dendritic spines using a fluorescence resonance energy transfer (FRET) technique.

Research Products

• [Journal Article] Activity-dependent gene regulation : How do synapses talk to the nucleus and fine-tune neuronal outputs? (2007)
  • Author(s): Bito H, Takemoto-Kimura S, Okuno H.
  • Journal Title: in "Molecular Pain" (M. Zhuo ed.) ( Springer) (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Activity-dependent gene regulation : How do synapses talk to the nucleus and fine-tune neuronal outputs? (2007)
  • Author(s): Bito H, Takemoto-Kimura S, Okuno H.
  • Journal Title: in "Molecular Pain" (M. Zhuo ed. Springer) (in press)
• [Journal Article] CREB1. (2006)
  • Author(s): Okuno, H., Bito H.
  • Journal Title: AfCS/Nature Molecule Pages (On-line)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Arc interacts with the endocytic machinery to regulate AMPA receptor trafficking. (2006)
  • Author(s): Chowdhury S, Shepherd JD, Okuno H, Lyford G, Petralia RS, Plath N, Kuhl D, Huganir RL, Worley PF.
  • Journal Title: Neuron 52 Pages: 445-459
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Molecular identification and characterization of a family of kinases with homology to CaMKI/CaMKIV. (2006)
  • Author(s): Ohmae S, Takemoto-Kimura S, Okamura M, Adachi-Morishima A, Nonaka M, Fuse T, Kida S, Tanji M, Furuyashiki T, Arakawa Y, Narumiya S, Okuno H, Bito H.
  • Journal Title: J. Biol. Chem 281 Pages: 20427-20439
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] CREB1. (2006)
  • Author(s): Okuno H, Bito H.
  • Journal Title: AfCS/Nature Molecule Pages doi:10.1038/mp.a000690.01
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Arc interacts with the endocytic machinery to regulate AMPA receptor trafficking (2006)
  • Author(s): Chowdhury S, Shepherd JD, Okuno H, Lyford G, Petralia RS, Plath N, Kuhl D, Huganir RL, Worley PF.
  • Journal Title: Neuron 52 Pages: 445-459
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Molecular identification and characterization of a family of kinase with homology to CaMKI/CaMKIV. (2006)
  • Author(s): Ohmae S, Takemoto-Kimura S, Okamura M, Adachi-Morishima A, Nonaka M, Fuse T, Kida S, Tanji M, Furuyashiki T, Arakawa Y, Narumiya S, Okuno H, Bito H.
  • Journal Title: J.Biol.Chem 281 Pages: 204278-20439
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CREB1. (2006)
  • Author(s): Okuno, H., Bito H.
  • Journal Title: AfCS/Nature Molecule Pages on-line
• [Journal Article] Arc interacts with the endocytic machinery to regulate AMPA receptor trafficking. (2006)
  • Author(s): Chowdlhury S, Shepherd JD, Okuno H, Lyford G, Petralia RS, Plath N, Kuhl D, Huganir RL, Worley PF.
  • Journal Title: Neuron 52 Pages: 445-459
• [Journal Article] Molecular identification and characterization of a family of kinases with homology to CaMKI/CaMKIV. (2006)
  • Author(s): Ohmae S, Takemoto-Kimura S, Okumura M, Adachi-Morishima A, Nonaka M, Fuse T, Kida S, Tanji M, Furuyashiki T, Arakawa Y, Narumiya S, Okuno H, Bito H.
  • Journal Title: J. Biol. Chem 281 Pages: 20427-20439
• [Journal Article] Creb 1 (2006)
  • Author(s): Okuno, H., Bito, H.
  • Journal Title: AfCS-Nature Molecular Pages
• [Journal Article] Activity-dependent gene regulation : signaling from synapse to the nucleus. (2006)
  • Author(s): Bito, H., Takemoto-Kimura, S., Okuno, H.
  • Journal Title: In : Molecular Pain (Zhuo M., ed) in press
• [Journal Article] Activity-dependent gene regulation : How do synapses talk to the nucleus and fine-tune neuronal outputs?
  • Author(s): Bito H, Takemoto-Kimura S, Okuno H.
  • Journal Title: Molecular Pain (M.Zhuo ed. Springer) (in press)
  • Description: 「研究成果報告書概要(欧文)」より