1997 Fiscal Year Final Research Report Summary
Mechanisms of signalmtransduction of glutamate receptors
| Project/Area Number |
07044247
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
General medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
NAKANISHI Shigetada Kyoto University, Medicine, Professor, 医学研究科 (20089105)
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| 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
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| Project Period (FY) |
1995 – 1997
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| Keywords | glutamate receptor / intracellular signal transduction / yeast two-hybrid / AMPA receptor / metabotropic glutamate receptor / protein interaction / Ca^<2+> signal transduction / neurotransmitter secretion |
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| 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.
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