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Study of Functions and Role of Multiple Glutamate Receptors

Research Project

Project/Area Number 04044093
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionKyoto University

Principal Investigator

NAKANISHI Shigetada  Kyoto University Faculty of Medicine, 医学部, 教授 (20089105)

Co-Investigator(Kenkyū-buntansha) MORIYOSHI Koki  Kyoto University Faculty of Medicine, 医学部, 助手 (50263091)
BESSHO Yasumasa  Kyoto University Faculty of Medicine, 医学部, 助手 (70261253)
KAGEYAMA Ryoichiro  Kyoto University Faculty of Medicine, 医学部, 助教授 (80224369)
SEEBURG Pete  ハイデルベルグ大学, 分子生物学センター, 教授
桝 正幸  京都大学, 医学部, 助手 (20243032)
PETER H.Seeb  ハイデルベルグ大学, 分子生物学センター, 教授
PETER H Seeb  ハイデルベルグ大学, 分子生物学センター, 教授
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥20,100,000 (Direct Cost: ¥20,100,000)
Fiscal Year 1994: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1993: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1992: ¥6,700,000 (Direct Cost: ¥6,700,000)
Keywordsglutamate receptor / molecular diversity / NMDA receptor / visual transmission / olfactory transmission / memory / molecular cloning / gene targeting / メタボトロピック受容体 / 遺伝子工学 / 細胞内情報 / 神経細胞死 / 視覚と嗅覚伝達 / 記憶と学習
Research Abstract

Glutamate receptors can be classified as AMPA/kainate, NMDA and metabotropic (mGluR) receptors. The AMPA/kainate receptors and the NMDA receptors both act as glutamategated cation channels, whereas mGluRs modulate the production of second messengers via G proteins. We have cloned and characterized the NMDA receptors and mGluRs with the aid of our cloning strategy that combines electrophysiology and a Xenopus oocyte expression system. The collaborators of this project, Dr.Peter H.Seeburg and his colleagues, have succeeded in molecular cloning of A/K receptors. By exchanging information and collaborating with each other, we have elucidated the existence and structural characteristics of diverse members of glutamate receptors and have demonstrated some critical roles of glutamate receptors in brain function.
1) The NMDA receptors consist of two distinct types of subunits : NMDAR1 possessing all properties characteristic of the NMDA receptors and four NMDAR2 subunits conferring functional variability by different heteromeric formations. The A/K receptors consist of 9 subunits, 4 subunits exhibiting the AMPA selectivity and 5 subunits showing the kainate selectivity. The mGluRs form a family of at least eight different subtypes (mGluR1mGluR8) .
2) The second transmembrane segments of the NMDA and A/K receptors form a channel pore, and aspargine in these segments is essential for determination of ion selectivity and the action of channel blockers.
3) mGluR6 is responsible for synaptic transmission from photoreceptors to ON-bipolar cells and mediates a key process in segregating visual signals into ON-and OFF-pathways.
4) mGluR2 at the presynaptic site of granule cells in the accessory olfactory bulb modulates inhibitory GABA transmission to mitral cells and plays an important role in discriminating olfactory stimuli and evoking an olfactory memory formation.

Report

(3 results)
  • 1994 Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Yasunori Hayashi,D.E.Jane,et al.: "Analysis of agonist and antagonist activities of phenylglycine derivatives for different cloned metabotropic glutamate receptor subtypes." Journal of Neuroscience. 14. 3370-3377 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Akinori Nomura,et al.: "Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells." Cell. 77. 361-369 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hideto Kaba,et al.: "Induction of an olfactory memory by the activation of a metabotropic glutamate receptor." Science. 265. 262-264 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shigetada Nakanishi: "Metabotropic gluatmate receptors:synaptic transmission,modulation,and plasticity." Neuron. 13. 1031-1037 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Masu,et al.: "Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene." Cell. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] A.E.Busch,et al.: "Molecular basis of IsK protein regulation by oxidation and chelation." The Journal of Biological Chemistry. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yasunori Hayashi, D.E.Jane, et al.: "Analysis of agonist and antagonist activities of phenylglycine derivatives for different cloned metabotropic glutamate receptor subtypes." Journal of Neuroscience. 14. 3370-3377 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Akinori Nomura, et al.: "Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells." Cell. 77. 361-369 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hideto Kaba, et al.: "Induction of an olfactory memory by the activation of a metabotropic glutamate receptor." Science. 265. 262-264 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shigetada Nakanishi: "Metabotropic glutamate receptors : synaptic transmission, modulation, and plasticity." Neuron. 13. 1031-1037 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Masu, et al.: "Specific deficit of the ON response in visual transmission by targeted disruption of the mgluR6 gene." Cell. in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] A.E.Busch, et al.: "Molecular basis of IsK protein regulation by oxidation and chelation." The Journal of Biological Chemistry. in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yasunori Hayashi,et al.: "Role of metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb." Nature. 366. 687-690 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ulrik Gether,et al.: "Different binding epitopes on the NK receptor for substance P and a non-peptide antagonist." Nature. 362. 345-348 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshiaki Nakajima,et al.: "Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate." The Journal of Biological Chemistry. 268. 11868-11873 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naoyuki Okamoto,et al.: "Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction." The Journal of Biological Chemistry. 269. 1231-1236 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yasumasa Bessho,et al.: "Selective up-regulation of an NMDA receptor subunit mRNA in cultured cerebellar granule cells by K^+-induced depolarization and NMDA treatment." Neuron. 12. 87-95 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akinori Nomura,et al.: "Developmentally regulated,postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells." Cell. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shigetada NAKANISHI: "Molecular diversity of glutamate receptors and implications for brain function." Science. 258. 597-603 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yasuto TANABE: "A family of metabotropic glutamate receptors." Neuron. 8. 169-179 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takaaki ABE: "Molecular characerization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca^<2+> signal transduction." The Journal of Biological Chemistry. 267. 13361-13368 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yasunori HAYASHI: "Agonist analysis of 2-(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells." British Journal of Pharmacology. 107. 539-543 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ichiro ARAMORI: "Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor mGluRl in transfected Chinese hamster ovary cells." Neuron. 8. 757-765 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ulrik Gether: "Different binding epitopes for substance P and the non-peptide antagonist, CP 96,345,on the NK_1 receptor." Nature.

    • Related Report
      1992 Annual Research Report
  • [Publications] 中西 重忠: "脳のはたらき-回路網・遺伝子・機能分子をめぐって-(3章分担:神経伝達の受容機構-グルタミン酸受容体とその受容機構を中心に-)" 講談社サイエンティフィク(伊藤正男/編), 30 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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