| Project/Area Number |
19209002
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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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)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥49,140,000 (Direct Cost: ¥37,800,000、Indirect Cost: ¥11,340,000)
Fiscal Year 2009: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2008: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2007: ¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000)
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| Keywords | plexin / semaphorin / R-Ras / M-Ras / Rho / 軸索ガイダンス / セマフォリン / Plexin / PTEN / PI3キナーゼ / カゼインキナーゼ / 神経軸索 / GAP / Rnd / サブグループ / 神経細胞 / Semaphorin / 成長円錐 |
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| Research Abstract |
Plexins are receptors for axonal guidance molecules semaphorins. We recently reported thet the Sema4D receptor, Plexin-B1, suppresses PI3 kinase signaling through R-Ras GAP activity, inducing growth cone collapse. PIP3 level is critically regulated by PI3 kinase and PTEN. 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. On the other hand, the expression of M-Ras, another member of R-Ras subfamily, is upregulated during dendritic development, and M-Ras is required for the denrite outgrowth. Sema4D/Plexin-B1 shows M-Ras GAP activity and suppresses dendrite outgrowth through M-Ras GAP acitivty. Thus, Plexin-B1 is a dual functional GAP for R-Ras and M-Ras, remodeling axon and dendrite morphology, respectively.
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