Grant-in-Aid for Overseas Scientific Survey.
|Research Institution||Kyoto University|
NAKANISHI Shigetada Kyoto University Faculty of Medicine, 医学部, 教授 (20089105)
影山 龍一郎 京都大学, 医学部, 助教授 (80224369)
PETER H Seeb 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
森吉 弘毅 京都大学, 医学部, 助手 (50263091)
別所 康全 京都大学, 医学部, 助手 (70261253)
SEEBURG Pete ハイデルベルグ大学, 分子生物学センター, 教授
MORIYOSHI Koki Kyoto University Faculty of Medicine
KAGEYAMA Ryoichiro Kyoto University Faculty of Medicine
BESSHO Yasumasa Kyoto University Faculty of Medicine
|Project Fiscal Year
1992 – 1994
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)
|Keywords||glutamate receptor / molecular diversity / NMDA receptor / visual transmission / olfactory transmission / memory / molecular cloning / gene targeting / グルタミン酸受容体 / 分子多様性 / NMDA受容体 / 視覚情報伝達系 / 嗅覚情報伝達系 / 記憶 / 遺伝子クローニング / 遺伝子破壊 / 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|
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.