| Project/Area Number |
24700392
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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 | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
WATANABE Hayaki 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 研究員 (70595587)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | Dock3 / 緑内障 / アクチン / Dockファミリー / 神経栄養因子 / small G protein / 神経変性疾患 |
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| Research Abstract |
Dock3, a new member of the guanine nucleotide exchange factor family, causes cellular morphological changes by activating the small GTPase Rac1. Overexpression of Dock3 in neural cells promotes neurite outgrowth through the formation of a protein complex with Fyn and WAVE downstream of brain-derived neurotrophic factor (BDNF) signaling. we found a novel Dock3-mediated BDNF pathway for neurite outgrowth. Dock3 forms a complex with Elmo and activated RhoG downstream of BDNF-TrkB signaling and induces neurite outgrowth via Rac1 activation in PC12 cells. In addition, Dock3 phosphorylation in Rac1 activation is important. We found that two key events that are necessary for efficient Dock3 phosphorylation, membrane recruitment of Dock3 and interaction of Dock3 with Elmo. These results suggest that Dock3 plays important roles downstream of BDNF signaling in the central nervous system where it stimulates actin polymerization by multiple pathways.
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