2009 Fiscal Year Final Research Report
A role of small GTPases in the formation of neural network system
| 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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| Keywords | plexin / semaphorin / R-Ras / M-Ras / Rho / 軸索ガイダンス |
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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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Research Products
(16 results)
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[Journal Article] Rac-GAP a-chimerin regulates motor-curcuit formation as a key mediator of Ephrin B3/EphA4 forward signaling.2007
Author(s)
Iwasato, T., Katoh, H., Nishimaru, H., Ishikawa, Y., Inoue, H., Saito, Y., Ando, R., Iwama, M., Takahashi, R., Negishi, M., Itohara, S.
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Journal Title
Peer Reviewed
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[Journal Article] Interaction of arginine-rich pepetides with membrane-associated proteoglycans is crucial for induction of actin organization and macropinocytosis.2007
Author(s)
Nakase, I., Tadokoro, A., Kawabata, N., Takeuchi, T., Katoh, H., Hiramoto, K., Negishi, M., Nomizu, M., Sugiura, Y., Futaki, S.
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Journal Title
Biochemistry 46
Pages: 492-501
Peer Reviewed
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