| Project/Area Number |
13480256
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Kyoto University |
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Principal Investigator |
NEGISHI Manabu Kyoto Univ., Grad.Sch.Biostudies, Professor, 生命科学研究科, 教授 (60201696)
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| Co-Investigator(Kenkyū-buntansha) |
KATOH Hironori Kyoto Univ., Grad.Sch.Biostudies, Instructor, 生命科学研究科, 助手 (50303847)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | neurite / Rho / Rnd / Plexin / Elmo / actin / microtubule / neuronal network / Rnd1 / RhoG / 軸索ガイダンス / Rnd2 / Rapostlin / 分枝化 / F-アクチン / 微小管 / Rac / NGF / Rhoキナーゼ / PC12細胞 / PI3キナーゼ |
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| Research Abstract |
The organization of the nervous system is a complex and orchestrated process. These dynamic morphological changes. of neurons are largely decided by the cytoskeletal organization. Rho family GTPases have been implicated in the regulation of the cytoskeleton and subsequent morphological changes in neurons. Among various Rho family GTPases, Rho induces neurite retraction, while Rac and Cdc42 are involved in neurite outgrowth. However, neural functions of other Rho family GTPases have not yet well investigated. We have examined the role of RhoG and found that RhoG induces neurite outgrowth by activating Rac and Cdc42 in PC12 cells. Furthermore, we identified Elmo as a novel effector of RhoG and revealed that RhoG. activates Rac 1 by direct interaction Elmo with Dock 180, inducing. neurite outgrowth. Next, we examined neuronal function of Rnd subfamily. We then found that Rnd1 binds to Plexin-B1, a receptor for axon guidance factor, Sema4D and induces cell retraction by promoting the binding of PDZ-RhoGEF to Plexin-B 1. We have screened the binding partner of Rnd2 and identified Rapostlin, a novel effector of Rnd2. Rapostlin has FCH domain at the N-terminus and SH3 domain at the C-terminus and regulates reorganization of both microtubule and actin cytoskeleton. Rapostlin induces neurite branching in response to Rnd2.
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