| Project/Area Number |
17079003
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
NEGISHI Manabu Kyoto University, 生命科学研究科, 教授 (60201696)
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| Co-Investigator(Kenkyū-buntansha) |
KATOH Hironori 京都大学, 生命科学研究科, 准教授 (50303847)
OINUMA Izumi 京都大学, 生命科学研究科, 助教 (40452297)
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| Project Period (FY) |
2005 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥78,900,000 (Direct Cost: ¥78,900,000)
Fiscal Year 2009: ¥16,900,000 (Direct Cost: ¥16,900,000)
Fiscal Year 2008: ¥16,900,000 (Direct Cost: ¥16,900,000)
Fiscal Year 2007: ¥16,900,000 (Direct Cost: ¥16,900,000)
Fiscal Year 2006: ¥18,800,000 (Direct Cost: ¥18,800,000)
Fiscal Year 2005: ¥9,400,000 (Direct Cost: ¥9,400,000)
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| Keywords | plexin / semaphorin / R-Ras / Rho / 軸索ガイダンス / ephrin / Myo-7 / インテグリン / FERM / モーター / ミオシン / 低分子量G蛋白 / 細胞運動 / M-Ras / 樹状突起 / 神経軸索 / 神経細胞 / GAP / Semaphorin / Plexin / Rnd1 / Plcxin / 成長円錐 / 神経回路 / 神経突起 / Plexon |
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| Research Abstract |
Small GTPases play important roles in the formation of neural network, especially axon guidance. We recently reported that the Sema4D receptor, Plexin-B1, suppresses PI3 kinase signaling through R-Ras GAP activity, inducing growth cone collapse. We then revealed that Sema4D/Plexin-B1 suppresses PI3 kinase activity but stimulates PTEN activity, leading to Akt activity suppression, GSK3b activation and CRMP-2 phosphorylation and then promotes growth cone collapse in hippocampal neurons. Sema4D/Plexin-B1 suppresses the ECM-dependent R-Ras activation and R-Ras-mediated integrin activation through R-Ras GAP activity. We also revealed that R-Ras binds to Myo7a and stimulates its motor activity, promoting trafficking integrin to the leading edge of plasma membrane and then induces resultant integrin activation. We here propose that Sema4D/Plexin-B1 suppresses R-Ras-mediated Myo7a stimulation and trafficking integrin to the plasma membrane, leading to integrin inactivation and subsequent axon repulsion.
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