1994 Fiscal Year Final Research Report Summary
Study of Functions and Role of Multiple Glutamate Receptors
| Project/Area Number |
04044093
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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 Institution | Kyoto University |
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Principal Investigator |
NAKANISHI Shigetada Kyoto University Faculty of Medicine, 医学部, 教授 (20089105)
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| 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
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| Project Period (FY) |
1992 – 1994
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| Keywords | glutamate receptor / molecular diversity / NMDA receptor / visual transmission / olfactory transmission / memory / molecular cloning / gene targeting |
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| 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.
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