2001 Fiscal Year Final Research Report Summary
Molecular mechanisums of regulation of NMDA receptor by post-synaptic density proteins
| Project/Area Number |
12680755
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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) |
KO Ji-ai 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) |
2000 – 2001
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| Keywords | NMPA recptor / PSD-95 / MALS-2 / PDZ proteins / Xenopus oocyte / PKC / Src / insulin |
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| Research Abstract |
The NMDA receptors is essential for the induction of long term potentiation (LTP) which is thought to plays a key role in synaptic plasticity underlying memory and learning. The NMDA receptor usually makes the complex with post-synaptic density proteins including PSD-95. MALS-2 and α-actinin. It is unknown how those proteins regulate the channel activity of the NMDA receptor. In this study, we examined the effects of PSD-95 on four )ε1/ζ1, ε2/ζ1, ε3/ζ1 and ε4/ζ1) subtypes of the NMDA receptor by injection of PSD-95 CRNA into Xenopus oocytes expressing the receptors. We also examined the effects of another PDZ protein, MALS-2, on the channel activity of the NMDA receptor. PSD-95 inhibited the protein kinase C (PKC) - mediated potentiation ofε1/ζ1 and ε2/ζ1 and the Src-mediated potentiation of ε1/ζ1. It has been reported that insulin potentiates the currents of the ε1/ζ1, ε2/ζ1, ε3/ζ1 and ε4/ζ1. Co-expressing of PSD-95 eliminated the insulin-induced potentiation of all four subtypes. MALS-2 dose not eliminate the potentiation of the channels by PKC, Src and insulin. We demonstrated that post-synaptic density proteins, like PSD-95 and MALS-2, functionally modulate the channel activity of NMDA receptor.
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Research Products
(8 results)
