| Project/Area Number |
14380358
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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 | Osaka University |
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Principal Investigator |
INAGAKI Shinobu Osaka University, Graduate School of Medicine, Sch Allied Health Science, Professor, 医学系研究科, 教授 (90151571)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUYAMA Tomohiro Hyogo Medical School, Dept.Internal Medicine, Assistant Professor, 医学部, 講師 (10219529)
FURUYAMA Tatsuo Sonoda Wemens University, Faculty of Human Health, Associate Professor, 人間健康学部, 助教授 (20238702)
OHOKA Yoshiharu Osaka University, Graduate School of Medicine, Sch Allied Health Science, Research Associate, 医学系研究科, 助手 (60303971)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2002: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | semaphorin / plexin / brain / glia / regulation / infection / morphology / inflammation / ミクログリア / 運動能 / 細胞膜 / 受容体 / シグナル伝達 / 神経栄養因子 |
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| Research Abstract |
The semaphorins constitute a family of secreted and transmembrane molecules that serve as repulsive guidance cues for developing neurons by virtue of their ability to induce retracton of the axonal growth cones. The functions of semaphorins are mediated plexins. Out of plexins, plexinB binds Sema4D, a class 4 transmembrane semaphorin, and mediate its signals via the Rho family GTPase. 1)In this project, we first found that PDZ domain containing-RhoGEFs associate plexinB1 and B2, to mediate Sema4D signal to activate RhoA (ref 1). 2)Recently, semaphorins are implicated in many physiological functions, in addition to repulsive roles in axon guidance. Second, we identified that Sema4D had ability to induce extension of axonal growth (ref 2 and 3). PC12 cells and spinal ganglion neurons respond to Sema4D and stimulated extension of axons, when cells were cultured with added NGF, and when spinal ganglion neurons were cultured without antibodies against NGF that bind endogenous NGF to block NGF-action. Since spinal ganglion neurons express Sema4D and plexinB1, Sema4D appeared to function in an autocrine manner in these neurons. These results suggest that some semaphorin can also functions as attractive guidance cues. 3)Third, we identified PDZ-containing Rho-GEFs associate to LPA1 and LPA2 but not LPA3, GPCR type receptors for lisophophatidic acid(LPA), a serum-derived phospholipid (ref 8). LPA has ability to retract axonal growth. Our results suggest that PDZ-containing Rho-GEFs couples GPCRs and plexinB1 to mediate LPA signals as well as Sema4D signals, and suggest a future study in situ function in the brain. 4)We found that glia cells expressed plexinB1 and Sema4D was implicated in regulation of glial activation, suggesting that an important role of Sema4D by regulating glial function.
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