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Regulations of metabolic functions by electrical activities in central neurons of higher animals

Research Project

Project/Area Number 09480230
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SUGIYAMA Hiroyuki  Kyushu University, Faculty of Science, Professor, 大学院・理学研究科, 教授 (20124224)

Co-Investigator(Kenkyū-buntansha) KATO Akihiko  Kyushu University, Faculty of Science, Research Associate, 大学院・理学研究科, 助手 (80294875)
MINAKAMI Reiko  Kyushu University, School of Health Scinece, Associate Professor, 医療技術短期大学部, 助教授 (00239302)
ITO Isao  Kyushu University, Faculty of Science, Associate Professor, 大学院・理学研究科, 助教授 (20183741)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥4,100,000 (Direct Cost: ¥4,100,000)
Keywordsbrain / neuron / gene expression / electrophysiology / molecular biology / neuroplasticity / 遺伝子発見 / 電子生物学 / PCR法 / mRNA
Research Abstract

The goal of this study is to analyze how the electrophysiological activities regulate the metabolic functions of higher animal nerve cells. For this purpose, we focused on the vest gene, and studied the structure, mechanisms of regulation of its expression and functions of this gene. We (and a U. S. group) found that this gene was upregulated by electrophysiological activities such as LTP in the rat hippocampus. In this study, we found the followings :
1. This gene makes the family of three homologous genes (ves-1, 2 and 3), and ves1-1 and 2 have splice variants.
2. Only the short form variant ves1-1S is upregulated during LTP. All the other ves1 proteins are constitutively expressed.
3. All ves1 proteins can bind with metabotropic glutamate receptors at their N-terminal regions.
4. All ves1 proteins except ves1-1S can bind with each other at their C-terminal regions, whereas ves1-1S lacks this region and cannot bind.
5. In the regulations of the expression levels of ves1-1S, degradation processes by proteasomes play important roles.
6. Ves1-1S is distributed in cytosolic regions in neurons at rest, but becomes accumulated at postsynaptic regions when simulated by phorbol esters.
These results led us to the following hypothesis :
The long forms of ves1 proteins which are expressed constitutively make clusters of metabotropic glutamate receptors by binding with the receptors and by associating with each other. The short form variant ves1-1S, when induced by electrophysiological activities, can liberate the receptors from the clusters by binding to the receptors in a competitive manner with the long ves1 proteins, and this may help reorganization of synapses.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Yamashita, S.: "The Ga protein GL2a improves the ability to detect the subthreshold expressions of receptors linked to phospholipase C in Xenopus oocytes."Jpn. J. Physiol.. 47. 67-72 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito. I.: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor el or e2 subunit"J. Physiol. (Lond.). 500. 401-408 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Minakami, R.: "Phosphorylation and calmodulin binding of the metabotropic glutamate receptor subtype 5 (mGluR5) are antagonistic in vitro."J. Biol. Chem.. 272. 20291-20298 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, I: "Distribution and development of NMDA receptor activities at hippocampal synapses examined using mice lacking the e 1 subunt gene"Neurosci. Res.. 30. 119-123 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kasahara, J.: "Modulation of glutamate sensitivities by inhibitors of a protein kinase and a protein phosphatase in cultured rat Purkinje cells."Neurosci. Lett.. 247. 139-142 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kato, A.: "Novel members of the Vesl/Homer family of PDZ Proteins that bind metabotropic glutamate receptors"J. Biol. Chem.. 273. 23969-23975 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Osaki, T.: "Horseshoe crab hemcyte-derived antimicrobial polypeptides, tachystatins, with sequence similarity to spider neruotoxins."J. Biol. Chem.. 274. 26172-26178 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, I: "Input-specific targeting of NMDA receptor subtypes at mouse hoppocampal CA3 pyramidal neuron synapses."Neuropharmacology. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamashita: "The Ga protein GL2a improves the ability to defect the subthreshold expressions of receptors linked to phospholipase C in Xenopus oocytes"Jpn. J. Physiol.. 47. 67-72 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, I.: "Synapses-selective impairment of NMDA receptor functions in mice lacking NMDA receptor e1 ore 2 subunit"J. Physiol. (Lond.). 500. 401-408 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Minakami, R.: "Phosphorylation and calmodulin binding of the metabotropic glutamate receptor subtype 5 (mGluR5) are antagonistic in vitro"J. Biochem.. 272. 20291-20298 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, I.: "Distribution and development of NMDA receptor activities at hippocampal synapses examined using mice lacking the e1 subunit gene"Neurosci. Lett.. 30. 119-123 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kasahara, J.: "Modulation of glutamate sensitivities by inhibitors of a protein kinase and a protein phosphatase in cultured rat Purkinje cells"Neurosci. Lett.. 247. 139-142 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kato, A.: "Novel members of the Ves1/Homer family of PDZ proteins that bind metabotropic glutamate receptors"J. Biochem.. 273. 23696-23975 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Osaki, T.: "Horseshoe crab hemocyte-derived antimicrobial polypeptides, tachystatins, with sequence similarity to spider neruotoxins"J. Biochem.. 274. 26172-26178 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, I.: "Input-specific targeting of NMDA receptor subtypes at mouse hippocampal CA3 pyramidal neuron synapses"Neuropharmacology. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, I.: "Distribution and develoopment of NMDA receptor activities at hippocampal synapses examined using mice lacking the εl subuint gene"Neurosci.Res.. 30. 119-123 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kasahara,J.: "Modulation of glutamate sensitivities by inhibitors of a protein kinase and a protein phoshatase in cultured rat Purkinje cells."Neurosci.Lett.. 247. 139-142 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kato,A.: "Novel members of the Vesl/Homer family of PDZ proteins that bind metabotropic glutamtate receptors."J.Biol.Chem.. 273. 23969-23975 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Osaki,T.: "Horseshoe crab hemocyte-derived antimicrobial polypeptides, tachystains, with sequence similarity to spider neruotoxins."J.Biol.Chem.. 274. 26172-26178 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito, I.: "Input-specific targeting of NMDA receptor subtypes at mouse hippocampal CA3 pyramidal neuron synapses."Neuropharmacology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 水上令子: "メタボトロピック・グルタミン酸受容体"生体の科学. 49. 377-380 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 水上令子: "メタボトロピック受容体"ニューロサイエンス・イラストレイテッド. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito,I: "Distribution and development of NMDA receptor activities at hippocampal synapses examined using mice lacking the e1 subuint gene" Neurosci.Res. 30. 119-123 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kasahara,J: "Modulation of glutamate sensitivitvities by inhibitors of a protein kinase and a protein phosphatase in cultured rat purkinje cells" Neurosci.Lett. 247. 139-142 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kato A: "Novel members of the vesl/Homer family of PDZ proteins that bind metabotropic glutamate receptors" J.Biol.Chem. 273. 23969-23975 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 水上令子: "メタボトロピック・グルタミン酸受容体" 医学書院, 4 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamashita,S.: "The Ga protein GL2a improves the ability to detect the subthreshold expressions of receptors linked to phospholipase C in Xenopus oocytes." Jpn.J.Physiol.47. 67-72 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ito,I.: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor e1 or e2 subunit." J.Physiol.(Lond.). 500. 401-408 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Minakami,R.: "Phosphorylation and calmodulin binding of the metabotropic glutamate receptor subtype 5(mGluR5)are antagonistic in vitro." J.Biol.Chem.272. 20291-20298 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ito,I.: "Distribution and development of NMDA receptor activities at hippocampal synapses examined using mice lacking the el subuint gene." Neurosci.Res.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 水上令子: "メタボトロピック受容体" 蛋白質核酸酵素. 42. 295-301 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 水上令子: "メタボトロピックグルタミン酸受容体" 生体の科学. 48. 371-375 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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