2003 Fiscal Year Final Research Report Summary
Molecular mechanisms of regulation of NMDA receptor by protein-protein interactions
| Project/Area Number |
14580744
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
YAMADA Yasue Yamaguchi University, School of Medicine, Research associate, 医学部, 助手 (00166737)
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| Co-Investigator(Kenkyū-buntansha) |
AI Ko ji Yamaguchi University, School of Medicine, Research associate, 医学部, 助手 (70314797)
KIMURA Yoshihiro Yamaguchi University, School of Medicine, Assistant professor, 医学部, 講師 (90301308)
INUI Makoto Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (70223237)
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| Project Period (FY) |
2002 – 2003
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| Keywords | NMDA receptor / PSD-95 / MALS-2 / Xenopus oocyte / PKC / Src / PDZ domain / GKAP |
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| Research Abstract |
We investigated the effects of PSD-95 and other scaffold proteins on the NMDA receptors using Xenopus oocyte expression system
1) PSD-95 increased the current response of NR1/NR2A, NR1/NR2B and NR1/NR2D
2) Other scaffold protein, MALS-2 increased the current response of the NR1-NR2B receptor to L-glutamate as well as reduced the sensitivity of this receptor to L-glutamate. In contrast, the current response of the NR1-NR2A receptor was not increased by MALS-2
3) Construction of chimeras between MALS-2 and PSD-95 revealed that the first two PDZ domains and two NH2terminal cysteine residues (possible palmitoylation sites) are essential for the inhibitory effects of PSD-95 on protein kinase C-mediated potentiation of NR1-NR2A and NR1-NR2B channels, respectively. The second of the three PDZ domains of PSD-95 was required for its inhibition of Src-mediated potentiation of NR1-NR2A channels
4) The NMDA receptor binds PSD-95 which interacts with GKAP (Guanylate Kinase-domain Associated Protein) through the GK domain of PSD-95. We examined the effects of PSD-95 and GKAP on four subtypes of the NMDA receptor. GKAP together with PSD-95 potentiated that of NR1/NR2B but not of NR1/NR2A and NR/NR2D.The channel activity of NR1/NR2C was potentiated only in the co-presence of PSD-95 and GKAP
5) These results indicate that MALS-2, PSD-95 and GKAP modulate the channel activity of the NMDA receptor in the subtype-specific manner
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