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1997 Fiscal Year Final Research Report Summary

Mechanisms of signalmtransduction of glutamate receptors

Research Project

Project/Area Number 07044247
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field General medical chemistry
Research InstitutionKyoto University

Principal Investigator

NAKANISHI Shigetada  Kyoto University, Medicine, Professor, 医学研究科 (20089105)

Co-Investigator(Kenkyū-buntansha) MORIYOSHI Koki  Kyoto University, Medicine, assistant professor, 医学研究科, 助手 (50263091)
YOKOI Mineto  Kyoto University, Medicine, assistant professor, 医学研究科, 助手 (40283618)
SASAI Yoshiki  Kyoto University, Medicine, associate professor, 医学研究科, 助教授 (20283616)
CARON Marc G.  Duke University Medical Center, Howard Hughes Medical Institute, Professor, ハワードヒューズ医学研究所, 教授
Project Period (FY) 1995 – 1997
Keywordsglutamate receptor / intracellular signal transduction / yeast two-hybrid / AMPA receptor / metabotropic glutamate receptor / protein interaction / Ca^<2+> signal transduction / neurotransmitter secretion
Research Abstract

Glutamate receptors mediate most excitatory neurotransmission and are important for integrative brain function and neurodegeneration. This project was designed to make a collaborative work with Dr.Marc Caron in Duke Unversity, including one year stay of Dr.Caron's colleaque, Dr.Russel Nash, in our laboratory and directed to elucidation of regulatory mechanisms of intracellular signaling cascades of glutamate receptors. The results obtained from this project can be summarized as follows :
1. Two closely related metabotropic glutamate receptors, mGluR1 and mGluR5, are coupled to inositol triphosphate (IP_3)/Ca^<2+> signal transduction mechanism. We demonstrated that mGluR1 and mGluR5 expressed in the heterologous expression system evoke non-oscillatory and oscillatory Ca^<2+> responses to application of glutamate, respectively, and that these distinct responses result from the substitution of a single amino acid susceptible to protein kinase C phosphorylation. We also demonstrated that mGluR5 induces Ca^<2+> oscillation in cultured astrocytes via protein kinase C phosphorylation. This is the first example that defines the target protein and the underlying mechanism responsible for Ca^<2+> oscillation.
2. GluR2 is a key subunit that permeates Ca^<2+> in the AMPA receptor-channel complex. Using the yeast two-hybrid system, we indicated that the NSF protein that is involved in neurotransmitter secretion interacts selectively with GluR2 among the members of AMPA receptor subunits and enhances AMPA receptor channels in hippocampal pyramidal neurons. This finding demonstrates a direct linkage between excitatory receptors and neurotransmitter secretion.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] K. Takebayashi, et al.: "Conversion of ectoderm into a neural fate by ATH-3 a vertebrate basic helix-loop-helix gene homologous to Drosophila proneural gene atonal." EMBO J.16. 348-395 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Iwakabe, et al.: "Impairment of pupillary responses and optokinetic nystagmus in the mGluR6-deficient mouse." Neuropharmacology. 36. 135-143 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y. Ueda, et al.: "The mGluR6 5' upstream transgene sequence directs a cell-specific and developmentally regulated expression in retinal rod and ON-type cone bipolar cells." J. Neurosci.17. 3014-3023 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Nakanishi, et al.: "Functions and roles of glutamate receptors in synaptic transmission and plasticity." Cold Spring Harbor Symposia on Quantitative Biology. 61. 67-75 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Nakahara, et al.: "The metabotropic glutamate receptor mGluR5 induces calcium oscillations in cultured astrocytes via protein kinase C phosphorylation." J. Neurochem.69. 1467-1475 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Takebayashi, et al.: "Conversion of ectoderm into a neural fate by ATH-3, a vertebrate basic helix-loop-helix gene homologous to Drosophila proneural gene atonal." EMBO J.16. 384-395 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Iwakabe, et al.: "Impairment of pupillary responses and optokinetic nystagmus in the mGluR6-deficient mouse." Neuropharmacology. 36. 135-143 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Ueda, et al.: "The mGluR6 5' upstream transgene sequence directs a cell-specific and developmentally regulated expression in retinal rod and ON-type cone bipolar cells." J.Neurosci.17. 3014-3023 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Nakanishi, et al.: "Functions and roles of glutamate receptors in synaptic transmission and plasticity." Cold Spring Harbor Symposia on Quantitative Biology. 61. 67-75 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Nakahara, et al.: "The metabotropic glutamate receptor mGluR5 induces calcium oscillations in cultured astrocytes via protein kinase C phosphorylation." J.Neurochem.69. 1467-1475 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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