| Project/Area Number |
23390019
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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 |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
NEGISHI MANABU 京都大学, 生命科学研究科, 教授 (60201696)
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| Co-Investigator(Renkei-kenkyūsha) |
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) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2011: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | plexin / semaphorin / R-Ras / M-Ras / Rho / 軸索 / 樹状突起 / 神経突起 / Rac / Rhoファミリー / スパイン / semapohorin / Plexin / Rnd / p190RhoGAP / ラフト / 突起伸長 / 突起退縮 / 細胞膜 |
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| Research Abstract |
Plexins are receptors for axonal guidance molecules semaphorins. We recently reported that the Sema4D receptor, Plexin-B1, functions as a GAP for R-Ras/M-Ras, inducing repulsion of both axons and dendrites, respectively. We have examined downstream effectors of R-Ras/M-Ras, linking to regulation of actin filament cytoskeleton, and we identified lamellipodin (lpd), a regulator of actin polymerization, as a novel effector of R-Ras/M-Ras. R-Ras/M-Ras specifically bind to lpd and recruite it to membranes, and Sema4D/Plexin-B1 suppresses R-Ras/M-Ras activity and lpd membrane translocation, inducing repulsion of axons and dendrite in hippocampal and cortical neurons. Our study shed light on how repulsive guidance molecules regulate actin cytoskeleton, revealing a novel mechanism that the R-Ras/M-Ras-lpd systems regulate actin-based axon and dendrite remodeling by sema/plexin in the formation of neural network system.
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