Live-cell imaging studies of central nervous system synapse formation and alteration.
| Project/Area Number |
17590152
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
INOUE Akihiro Tokyo Medical and Dental University, Graduate School, Associate Professor, 大学院医歯学総合研究科, 助教授 (80322080)
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| Co-Investigator(Kenkyū-buntansha) |
OKABE Shigeo Tokyo Medical and Dental University, Graduate School, Professor, 大学院医歯学総合研究科, 助教授 (60204012)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | synapse scaffolding protein / virus vector / RNA interference / green fluorescent protein / post synaptic density / actin / hippocampal culture / fluorescent recovery after photobleaching / シナプス形成 / トランスジェニックマウス / 脳組織器官培養標本 / 二光子レーザー顕微鏡 |
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| Research Abstract |
Organization and dynamic remodeling of postsynaptic density (PSD) are thought to be important for postsynaptic signal transduction. To study the molecular mechanisms, we performed live-cell imaging analyses of dynamic characteristics of major PSD proteins both at steady state and when neurons are activated by exogenous stimulations.
Cortactin is an F-actin-associated protein which interacts with the postsynaptic scaffolding protein Shank and is localized within the dendritic spine. Green fluorescent protein (GFP)-based time-lapse imaging revealed cortactin redistribution from dendritic cytoplasm to postsynaptic sites by application of brain-derived neurotrophic factor (BDNF). In contrast, activation of N-methyl-d-aspartate (NMDA) receptors induced loss of cortactin from postsynaptic sites. These results indicate the importance of counterbalance between BDNF and NMDA receptor-mediated signaling in the reorganization of the postsynaptic actin cytoskeleton during neuronal development.
We also reported that four major scaffolding molecules, PSD-95, GKAP, Shank, and PSD-Zip45, show distinct instability in total molecular content per synapse. Fluorescence recovery after photobleaching (FRAP) also confirmed their distinct turnover rates. Among the PSD molecules examined, PSD-95 was most stable. Acute pharmacological disruption of F-actin eliminated the dynamic fraction of GKAP, Shank, and PSD-Zip45. GKAP content in synapses increased after pharmacological enhancement of neuronal activity, on the other hand Shank and PSD-Zip45 content are reduced. Inhibition of F-actin dynamics prevented activity-dependent redistribution of all three scaffolds. These results indicate that F-actin plays a key role for regulating the dynamic reorganization molecular composition in PSD.
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Myosin-Va facilitates the accumulation of mRNA/protein complex in dendritic spines.2006
Author(s)
Yoshimura, A., Fujii, R., Watanabe, Y., Okabe, S., Fukui, K., T.Takumi
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Journal Title
Current Biology 16
Pages: 2345-2351
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Telencephalin slows spine maturation.2006
Author(s)
Matsuno, H., Okabe, S., Mishina, M., Yanagida, T., Mori, K., Y.Yoshihara
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Journal Title
Journal of Neuroscience 26
Pages: 1776-1786
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The RNA-binding protein TLS is translocated to dendritic spines by mGluR5 activation and regulates spine morphology.2005
Author(s)
Fujii, R.*, Okabe, S.*, Urushido, T., Inoue, K., Tachibana, T., Nishikawa, T., Hick, G.G., T.Takumi.(* equal contribution.)
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Journal Title
Current Biology 15
Pages: 587-593
Description
「研究成果報告書概要(欧文)」より
Related Report
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