| Project/Area Number |
18300107
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Nara Institute of Science and Technology |
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Principal Investigator |
INAGAKI Naoyuki Nara Institute of Science and Technology, Biological Sciences, Associate Professor (20223216)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Tadayuki Nara Institute of Science and Technology, Biological Sciences, Assistant Professor (80379552)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2007: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2006: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Neuron / Cell polarity / Axon / Dendrite / Shootin1 / L1 / Actin / Growth cone / Shootin1 / Wave / PI 3-kinase / ノックアウトマウス |
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| Research Abstract |
The basic function of neurons is to receive, integrate and transmit signals. To do so, most neurons develop polarity by forming a single axon and multiple dendrites. Neurons have the remarkable ability to polarize even in symmetrical in vitro environments. Although recent studies have shown that asymmetric intracellular signals can induce neuronal polarization, it remains unclear how these polarized signals are organized without asymmetric cues. We recently described an intracellular protein, shootin1, which plays a critical role in neuronal polarization. During the symmetry breaking step, shootin1 becomes up-regulated, undergoes a fluctuating accumulation in growth cones at neurite tips, and eventually accumulates asymmetrically in a single growth cone. Accumulation of shootin1 in nerve growth cones also enhanced neurite elongation. In this study, we examined molecular mechanisms for shootin1-induced neurite outgrowth and the mechanisms for generation of asymmetric signal of shootin1. Shootin1 not only acted as a upstream regulator of PI 3-kinase but also enhanced neurite elongation, by linking a cell adhesion molecule Ll-CAM to actin filament retrograde flow as a "clutch molecule". We also obtained data to suggest that positive feedback amplification of shootin1 signal in growth cones contributes to generation of asymmetric shootin 1 signals during neuronal polarization. We also succeeded in generation of shootin 1 knockout mice, and are currently analyzing their phenotypes.
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