| Project/Area Number |
26830045
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Nagoya University |
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Principal Investigator |
Tetsuya Takano 名古屋大学, 医学(系)研究科(研究院), 研究員 (00725541)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | Neuronal polarity / RhoA / Rho-kinase / CaMKI / 神経極性 / 発生 / 細胞極性 / 軸索形成 / 樹状突起形成 |
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| Outline of Final Research Achievements |
Neurons are highly polarized cells, which have two structurally and functionally distinct compartments, ie., axons and dendrites. Neuronal polarization is precisely established by local activation signal and long-range inhibitory signaling (Takano et al., 2015, Development). However, the long-range inhibitory signaling that prevents multiple axonal formation remains largely unknown.
In this year, we found that local application of NT-3 to axon induced a long-range Ca2+ propagation that led to activate RhoA in the cell body through CaMKI. The local inhibition of Rho-kinase in the minor neurites induced neurite elongation and subsequently formed multiple axons. We performed phospho-proteomic analysis (the KISS method) to identify novel substrates for CaMKI. We found that CaMKI phosphorylated a RhoGEF, and enhanced its GEF activity. Together, long-range signaling of Ca2+/CaMKI/RhoGEF/RhoA/Rho-kinase might be a novel inhibitory pathway responsible for neuronal polarization.
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