Project/Area Number |
17500252
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
|
Research Institution | Shinshu University |
Principal Investigator |
SUZUKI Tatsuo Shinshu University, Graduate School of Medicine, Professor, 大学院医学研究科, 教授 (80162965)
|
Co-Investigator(Kenkyū-buntansha) |
TIAN Qing Bao Shinshu University, Graduate School of Medicine, Assistant professor, 大学院医学研究科, 講師 (40324264)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | PSD / dendritic mRNA / novel gene / synapse / postsynaptic density / synaptic plasticity / memory and learning / neuronal diseases / LRP4 / postsynaptic density / lipid raft / calmodulin kinase II / cluster formation / gene chip / local protein synthesis / synaptic plastcity / molecular mechanism |
Research Abstract |
We cloned various novel genes of which mRNAs are localized in the postsynaptic compartments, and which are translated and targeted to postsynaptic sites. We further characterized their nature and functions in vivo. 1. We produced targeting vectors for LRP4 (LDL receptor-related protein 4) and synUSP (synaptic Ubiquitin-specific protease). We continue to make knockout mice for these genes. We identified apoE as a ligand for LRP4. In addition, we also identified another LRP4 ligand and suggested a. role of LRP4 in axon guidance. 2. Using antibody towards ligand-binding domain of LRP4, we suggested that LRP4 is involved in synaptic differentiation and neuronal survival. 3. We analyzed mRNA species that are associated with postsynaptic density (PSD) fraction by using gene chip microarray. In the study we identified about 1,900 mRNA species that are highly concentrated to the PSD fraction. We also identified localization of neuronal disease-related mRNAs at the postsynaptic site. 4. We demonstrated at the electron microscopic level that p55 protein is localized to PSD. 5. We characterized IQ-ArfGEF/BRAG1, which is closely related to aynArfGEF/BRAG3. 6. We found that cluster formation of CaMKII occurs in lipid raft microdomains.
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