Investigation for the mechanism of synapse formation by regenerated neurons.

• Project/Area Number: 20890113
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Osaka University
• Principal Investigator: HATA Katsuhiko Osaka University, 医学系研究科, 助教 (60506228)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,302,000 (Direct Cost: ¥2,540,000、Indirect Cost: ¥762,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,742,000 (Direct Cost: ¥1,340,000、Indirect Cost: ¥402,000)
• Keywords: 中枢神経 / 再生医療 / シナプス / 軸索 / 再生阻害蛋白質 / RGM / 機能回復 / 脊髄 / 脊髓

Research Abstract

Synapse formation of the cortico-spinal axons is enhanced by RGMa inhibition RGMa binding to its receptor neogenin induces RhoA activation, leading to inhibitory/repulsive behavior and collapse of the neuronal growth cone. However, the precise mechanisms that regulate RhoA activation are poorly understood. In this study, we show that Unc5B, a member of the netrin receptor family, interacts with neogenin as a coreceptor for RGMa. Moreover, leukemia-associated guanine nucleotide exchange factor (LARG) associates with Unc5B to transduce the RhoA signal. Focal adhesion kinase (FAK) is involved in RGMa-induced tyrosine phosphorylation of LARG as well as RhoA activation. These findings uncover the molecular basis for inhibition of synapse formation mediated by RGMa.

Research Products

• [Journal Article] Transplantation of whole-layer olfactory mucosa promotes restricted functional recovery in rats with complete spinal cord injury. (2010)
  • Author(s): Aoki, M., Kishima, H., Yoshimura, Y., Ishihara, M., Ueno, M., Hata, K., Yamashita, T., Iwatsuki, K., Yoshimine, T.
  • Journal Title: Journal of Neurosurgery: Spine 12 Pages: 122-130
  • Peer Reviewed
• [Journal Article] Transplantation of whole-layer olfactory mucosa promotes restricted functional recovery in rats with complete spinal cord injury (2010)
  • Author(s): Aoki, M., Kishima, H., Yoshimura, Y., Ishihara, M., Ueno, M., Hata, K., Yamashita, T., Iwatsuki, K., Yoshimine, T
  • Journal Title: Journal of Neurosurgery : Spine 12 Pages: 122-130
  • Peer Reviewed
• [Journal Article] Zyxin is a novel interacting partner for SIRT1. (2009)
  • Author(s): Fujita, Y., Yamaguchi, A. Hata, K., Endo, M., Yamaguchi, N., Yamashita, T.
  • Journal Title: BMC Cell Biol. 10 Pages: 6-6
  • Peer Reviewed
• [Journal Article] Unc5B associates with LARG to mediate the action of repulsive guidance molecule. (2009)
  • Author(s): Hata, K., Kaibuchi, K., Inagaki, S., Yamashita, T.
  • Journal Title: J. Cell Biol. 184 Pages: 737-750
  • Peer Reviewed
• [Journal Article] Unc5B associates with LARG to mediate the action of repulsive guidance molecule (2009)
  • Author(s): Hata, K., Kaibuchi, K., Inagaaki, S., Yamashita, T.
  • Journal Title: J. Cell Biol. (In press)
  • Peer Reviewed
• [Journal Article] Zyxin is a novel interacting partner for SIRT1 (2009)
  • Author(s): Fujita, Y., Yamaguchi, A. Hata, K., Endo, M., Yamaguchi, N., Yamashita, T.
  • Journal Title: BMC Cell Biol. (In press)
  • Peer Reviewed
• [Journal Article] Peptides derived from repulsive guidance molecule act as antagonists. (2008)
  • Author(s): Suda, M., Hata, K., Sawada, A., Nakamura, Y., Kubo., Yamaguchi, A., Yamashita, T.
  • Journal Title: Biochem Biophys Res Commun. 371 Pages: 501-504
  • Peer Reviewed
• [Journal Article] Myosin IIA is required forneurite outgrowth inhibition produced by RGMa. (2008)
  • Author(s): Kubo, T., Endo, M., Hata, K., Taniguchi, J., Kitajo, K., Tomura, S., Yamaguchi, A., Mueller, B.K., Yamashita, T.
  • Journal Title: J. Neurochem 105 Pages: 113-126
  • Peer Reviewed
• [Journal Article] BMP inhibition enhances axonal growth and functional recovery after spinal cord injury. (2008)
  • Author(s): Matsuura, I., Taniguchi, J., Hata, K., Saeki, N., Yamashita, T.
  • Journal Title: J. Neurochem. 105 Pages: 1471-1479
  • Peer Reviewed
• [Journal Article] Neogenin regulates neuronal survival through DAP-kinase. (2008)
  • Author(s): Fujita, Y., Taniguchi, J., Uchikawa, M., Endo, M., Hata, K., Kubo, T., Mueller, B.K., Yamashita, T.
  • Journal Title: Cell Death Differ 15 Pages: 1593-1608
  • Peer Reviewed
• [Journal Article] Peptides derived from repulsive guidance molecule act as antagonists (2008)
  • Author(s): Suda, M., Hata, K., Sawada, A., Nakamura, Y., Kubo., Yamaguchi, A., Yamashita, T.
  • Journal Title: Biochem Biophys Res Commun. 371 Pages: 501-504
  • Peer Reviewed
• [Journal Article] Neogenin regulates neuronal survival through DAP-kinase. (2008)
  • Author(s): Fujita, Y., Taniguchi, J., Uchikawa, M., Endo, M., Hata, K., Kubo, T., Mueller, B. K., Yamashifa, T.
  • Journal Title: Cell Death Differ. 15 Pages: 1593-1608
  • Peer Reviewed
• [Journal Article] Neogenin regulates neuronal survival through DAP-kinase. (2008)
  • Author(s): Fujita, Y., Taniguchi, J., Uchikawa, M., Endo, M., Hata, K., Kubo, T., Mueller, B. K., Yamashita, T.
  • Journal Title: Cell Death Differ. 15 Pages: 1593-1608
  • Peer Reviewed
• [Presentation] Unc5BはLARGと結合し、RGMのシグナルを伝達する (2009)
  • Author(s): 羽田克彦、山下俊英
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2009-09-18
• [Presentation] 新機軸策再生阻害因子のシグナル伝達機構 (2009)
  • Author(s): 羽田克彦、山下俊英
  • Organizer: 日本分子生物学会第9回春季シンポジウム
  • Place of Presentation: 宮崎市
  • Year and Date: 2009-05-11
• [Presentation] 新規軸索再生阻害因子のシグナル伝達機構 (2009)
  • Author(s): 羽田克彦、山下俊英
  • Organizer: 日本分子生物学会第9回春季シンポジウム
  • Place of Presentation: 宮崎市
• [Presentation] RGMaの細胞内シグナル伝達機構 (2008)
  • Author(s): 羽田克彦, 山下俊英
  • Organizer: BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] RGMaの細胞内シグナル伝達機構 (2008)
  • Author(s): 羽田克彦, 山下俊英
  • Organizer: 日本神経化学会大会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-12
• [Presentation] RGMaの細胞内シグナル伝達機構 (2008)
  • Author(s): 羽田克彦, 山下俊英
  • Organizer: GRT
  • Place of Presentation: 千葉
  • Year and Date: 2008-05-17
• [Presentation] RGMaの細胞内シグナル伝達機構 (2008)
  • Author(s): 羽田克彦、山下俊英
  • Organizer: BMB2008
  • Place of Presentation: 神戸市
• [Presentation] RGMaの細胞内シグナル伝達機構 (2008)
  • Author(s): 羽田克彦、山下俊英
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山市
• [Presentation] RGMaの細胞内シグナル伝達機構 (2008)
  • Author(s): 羽田克彦、山下俊英
  • Organizer: 神経組織の成長・再生・移植研究会第23回学術集会
  • Place of Presentation: 千葉市