2009 Fiscal Year Final Research Report
A role of interactive actions of small GTPases in the formation of neural network
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 |
Review Section |
Biological Sciences
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Research Institution | Kyoto University |
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)
|
Project Period (FY) |
2005 – 2009
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Keywords | plexin / semaphorin / R-Ras / Rho / 軸索ガイダンス / ephrin |
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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[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] Sema4D/Plexin-B1 activates GSK-3βvia R-Ras GAP activity, inducing growth cone collapse.2006
Author(s)
Ito, Y., Oinuma, I., Katoh, H., Kaibuchi, K., Negishi, M.
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Journal Title
EMBO Rep. 7
Pages: 704-709
Peer Reviewed
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[Journal Article] In vivo function of Rnd2 in the development of neocortical pyramidal neurons.2006
Author(s)
Nakamura, K., Yamashita, Y., Tamamaki, N., Katoh, H., Kaneko, T., Negishi, M.
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Journal Title
Neurosci. Res. 54
Pages: 149-153
Peer Reviewed
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