Project/Area Number |
09480230
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neuroscience in general
|
Research Institution | KYUSHU UNIVERSITY |
Principal Investigator |
SUGIYAMA Hiroyuki Kyushu University, Faculty of Science, Professor, 大学院・理学研究科, 教授 (20124224)
|
Co-Investigator(Kenkyū-buntansha) |
KATO Akihiko Kyushu University, Faculty of Science, Research Associate, 大学院・理学研究科, 助手 (80294875)
MINAKAMI Reiko Kyushu University, School of Health Scinece, Associate Professor, 医療技術短期大学部, 助教授 (00239302)
ITO Isao Kyushu University, Faculty of Science, Associate Professor, 大学院・理学研究科, 助教授 (20183741)
|
Project Period (FY) |
1997 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥4,100,000 (Direct Cost: ¥4,100,000)
|
Keywords | brain / neuron / gene expression / electrophysiology / molecular biology / neuroplasticity / 遺伝子発見 / 電子生物学 / PCR法 / mRNA |
Research Abstract |
The goal of this study is to analyze how the electrophysiological activities regulate the metabolic functions of higher animal nerve cells. For this purpose, we focused on the vest gene, and studied the structure, mechanisms of regulation of its expression and functions of this gene. We (and a U. S. group) found that this gene was upregulated by electrophysiological activities such as LTP in the rat hippocampus. In this study, we found the followings : 1. This gene makes the family of three homologous genes (ves-1, 2 and 3), and ves1-1 and 2 have splice variants. 2. Only the short form variant ves1-1S is upregulated during LTP. All the other ves1 proteins are constitutively expressed. 3. All ves1 proteins can bind with metabotropic glutamate receptors at their N-terminal regions. 4. All ves1 proteins except ves1-1S can bind with each other at their C-terminal regions, whereas ves1-1S lacks this region and cannot bind. 5. In the regulations of the expression levels of ves1-1S, degradation processes by proteasomes play important roles. 6. Ves1-1S is distributed in cytosolic regions in neurons at rest, but becomes accumulated at postsynaptic regions when simulated by phorbol esters. These results led us to the following hypothesis : The long forms of ves1 proteins which are expressed constitutively make clusters of metabotropic glutamate receptors by binding with the receptors and by associating with each other. The short form variant ves1-1S, when induced by electrophysiological activities, can liberate the receptors from the clusters by binding to the receptors in a competitive manner with the long ves1 proteins, and this may help reorganization of synapses.
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