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Physiological Significance of the extracellular Ca2+ Sensitivity of the Metabotropic Glutamate Receptor

Research Project

Project/Area Number 10480233
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field 神経・脳内生理学
Research InstitutionTokyo Medical and Dental Inversity graduate School (2000)
Tokyo Metropolitan Organization for Medical Research (1999)
Tokyo Metropolitan Institute for Neuroscience (1998)

Principal Investigator

KUBO Yoshihiro  Tokyo Medical and Dental University Graduate School Department of Physiology, Professor, 大学院・医歯学総合研究科, 教授 (80211887)

Co-Investigator(Kenkyū-buntansha) MIWA Akiko  Tokyo Metropolitan Institute for Neuroscience Dept.Molecular Physiology, Research Scientist, 東京都神経科学総合研究所, 主事研究員 (60142155)
OKADO Haruo  Tokyo Metropolitan Institute for Neuroscience Dept.Molecular Physiology, Senior Research Scientist, 東京都神経科学総合研究所, 副参事研究員 (60221842)
MIYASHITA Tomoyuki  Tokyo Metropolitan Institute for Neuroscience Dept.Molecular Physiology, Research Scientist, 東京都神経科学総合研究所, 主事研究員 (70270668)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1998: ¥8,200,000 (Direct Cost: ¥8,200,000)
Keywordsmetabotropic / glutamate / receptor / calcium / cAMP / グルタミン酸受容体 / カルシウム / cAMP / metabotropic / glutamate / recceptor / calcium / sensing
Research Abstract

We previously reported that the metabotropic glutamate receptor R1 a (mGluR1 α) can be activated not only by applying glutamate but also by raising extracellular Ca^<2+> (Ca^<2+>_0) concentration, and that the constant stimulation by Ca^<2+>_0 causes morphological change of transfected Chinese Hamster Ovary (CHO) cells. The physiological role of the Ca^<2+>_0-sensing function of mGluR1 α, however, is not fully clear yet, especially because Ca^<2+> is constitutively present an the extracellular space unlike other neurotransmitters. In this work, we aimed to elucidate the physiological significance of the Ca^<2+>_0-sensing function of mGluR1 α. The effect of mGluR1 α activation by Ca^<2+>_0on the morphological change of CHO cells was mimicked by forskolin. The effect of mGluR1 a activation on the morphological change was suppressed by the inhibitors of adenylate cyclase, protein kinase A (PKA) and MAP kinase kinase (MAPKK), and the effect of forskolin was also decreased by the inhibitors of PKA and MAPKK.These results demonstrate the involvement of cAMP, PKA, MAPKK, MARK pathway in the morphological change. We actually confirmed that the Ca^<2+>_0stimulation of mGluR1 α increased the basal cAMP level of transfected CHO cells. This increase in cAMP was observed even when only the membrane fraction of mGluR1 a transfected CHO cells were used, and the increase was inhibited by anti-Gsα antibody. Taken together, we concl uded that the Ca^<2+>_0-sensing function of mGluR1 a and the continuous stimulation by Ca^<2+>_0 caused the increase in the basal cAMP level by direct coupling with Gs, and triggered the subsequent activation of PKA, MAPKK, and MAPK cascade which resulted in the morphological change of transfected CHO cells.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Kubo,Y.,Miyashita,T.and Murata.Y.: "Structural basis for a Ca2+-sensing function of the metabotropic glutamate receptors."Science. 279. 1722-1725 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saitoh,O.,kobo,Y.,Odagiri,M.,lchikawa,M.,Yamagata,k.and Sekine.J.: "RGS7 and RGS8 Differentially Accelerate G Protein-mediated Modulation of Kt Currents."Journal of Biological Chemistry. 274. 9899-9904 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyashita,T.and kubo,Y.: "Extracellular Ca2+ sensitivity of mGluR1α associated with persistent glutamate response in transfected CHO cells."Receptors and Channels. 7. 25-40 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyashita,T.and kubo,Y.: "Extracellular Ca2+ sensitivity of mGluR1α induces an increase in the basal cAMP level.by direct coupling with Gs protein in transfected CHO cells."Receptors and Channels. 7. 77-91 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubo,Y.and Murata,Y.: "Control of rectification and permeation by two distinct sites after the second transmembrane region in kir2.1 kt channel."Journal of Physiology. 531. 645-660 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saitoh,o.,Masuho,l.,Terakawa,l.,Nomoto,S.,Asano,T.and kubo,Y.: "RGS8 requires its N-terminus for subcellular localization and acute desensitization of G protein gated k+ channels."Journal of Biological Chemistry. 276. 5052-5058 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubo, Y., Miyashita, T.and Murata, Y.: "Structure basis for a Ca^<2+>-sensing function of the metabotropic glutamate receptors."Science. 279. 1722-1725 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saitoh, O., Kubo, Y., Odagiri, M., Ichikawa, M., Yamagata, K.and Sekine, T.: "RGS7 and RGS8 Differentially Accelerate G Protein-mediated Modulation of K^+ Currents."Journal of Biological Chemistry. 274. 9899-9904 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyashita, T.and Kubo, Y.: "Extracellular Ca^<2+> sensitivity of mGluR1α associated with persistent glutamate response in transfected CHO cells."Receptors and Channels. 7. 25-40 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyashita, T.and Kubo, Y.: "Extracellular Ca^<2+> sensitivity of mGluR1α induced an increase in the basel cAMP level by direct coupling with Gs protein in trasfected CHO cells."Receptors and Channels. 7. 77-91 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubo, Y.and Murata, Y.: "Control of rectification and permeation by two distinct sites after the second transmembrane region in Kir2.1 K^+ channel."Journal of Physiology. 531. 645-660 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saitoh, O., Masuho, I., Terakawa, I., Nomoto, S., Asano, T.and Kubo, Y.: "RGS8 requires its N-terminus for subcellular localization and acute desensitization of G protein gated K^+ channels."Journal of Biological Chemistry. 276. 5052-5058 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Soom, M., Schonherr, R., Kubo, Y., Kirsch, C., Klinger, R.and Heinemann, S.H.: "Multiple PIP_2 binding sites in Kir2.1 inwardly rectifying potassium channels."FEBS letters. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murata,Y.,Okado,H.and Kuto,Y: "Characterization of heteromultimetric G-proton coupled inwardly rectifying potassium channels of the tunicate tadpole with a unique pore property."Journal of Biological Chemistry. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Saitoh, O., Masuho, I., Terakawa, I., Nomoto, S., Asano, T. and Kubo, Y.: "RGS8 requires its N-terminus for subcellular localization and acute desensitization of G protein gated k^+ channels."Journal of Biological Chemistry. 276. 5052-5058 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kubo,Y.and Murata,Y.: "Control of rectification and permeation by two distinct sites after the second transmembrane region in Kir2.1 K+ channel."Journal of Physiology. 531. 645-660 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Soom.,M.,Schonherr,R.,Kubo,Y.,Kirsch,C.,Klinger,R.and Heinemann.S.H: "Multiple PIP2 binding sites in Kir2-1 inwardly rectifying potassium channels."FEBS Ietters. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyashita,T.and Kubo,Y.: "Extracellular Ca^<2+> sensitivity of mGluR1a induces an increase in the basal cAMP level by direct coupling with Gs protein in transfected CHO cells"Receptors and Channels. 7. 77-91 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyashita,T and Kubo,Y.: "Extracellular Ca^<2+> sensitivity of mGluR1a ssociated with persistent glutamate response in transfected CHO cells"Receplors and Channels. 7. 25-40 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T. M. Yashita & Y. Kubo: "Extracellular Ca^<2+> sensivity of malnR12 associated with persistence glntamagic response in cranstected CHO cells"Receptors & Channels. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. M. Yashita & Y. Kubo: "Extracellular Ca^<2+> sensivity of malnR12 induces an increase in chc hasal CAMP lekl bydirect conpling with Gs protein in transferred CHD cells"Receptors & Channels. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kubo,Miyashita,Murata: "Structaral basis for a Ca^<2+> sensing Junction of the metabotripic glutamate receptions" Science. 299. 1722-1725 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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