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Molecular mechanisms for LPA_3-mediated neurite branch formation

Research Project

Project/Area Number 21590109
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKinki University

Principal Investigator

FUKUSHIMA Nobuyuki  近畿大学, 理工学部, 講師 (10254161)

Co-Investigator(Renkei-kenkyūsha) TSUJIUCHI Toshifumi  近畿大学, 理工学部, 教授 (10254492)
MORIYAMA Ryutaro  近畿大学, 理工学部, 講師 (30411573)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsリゾホスファチジン酸 / G蛋白質 / 神経軸索 / 分岐 / 神経ネットワーク / LPA3 / 神経分岐 / Rnd2 / リゾホスファジン酸
Research Abstract

Although neurite branching is crucial for neuronal network formation after birth, its underlying mechanisms remain unclear. Here, we demonstrate that lysophosphatidic acid(LPA) stimulates neurite branching through a novel signaling pathway. Treatment of neuronal cell lines with LPA resulted in neurite branch formation when LPA_3 receptor was introduced. The effects of LPA were blocked by inhibition of G_q signaling. Furthermore, expression of inhibitory mutants of the small GTPase Rnd2/Rho7 or an Rnd2 effector rapostlin abolished LPA_3-mediated neurite branching. The LPA_3 agonist 2(S)-OMPT or LPA also induced axonal branch formation in hippocampal neurons, which was blocked by G_q and Rnd2 pathway inhibition or LPA_3 knockdown. These findings suggest that the novel signaling pathway involving LPA_3, G_q, and Rnd2 may play an important role in neuronal network formation.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (25 results)

All 2012 2011 2010 2009 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (7 results) Book (1 results)

  • [Journal Article] Lysophosphatidic acid induces neurite branch formation through LPA_32012

    • Author(s)
      Furuta, D., Yamane, M., Tsujiuchi, T., Moriyama, R. and Fukushima, N
    • Journal Title

      Mol. Cell. Neurosci

      Volume: 50 Pages: 21-34

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential function of lysophosphatidic acid receptors in cell proliferation and migration of neuroblastoma cells2012

    • Author(s)
      Hayashi, M., Okabe, K., Kato, K., Okumura, M., Fukui, R., Fukushima, N. and Tsujiuchi, T
    • Journal Title

      Cancer Lett

      Volume: 316 Pages: 91-96

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lysophosphatidic acid induces neurite branch formation through LPA_32012

    • Author(s)
      Furuta, D., et al
    • Journal Title

      Mol.Cell.Neurosci.

      Volume: (印刷中) Issue: 1 Pages: 21-34

    • DOI

      10.1016/j.mcn.2012.03.006

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lysophosphatidic acid receptor-3 increases tumorigenicity and aggressiveness of rat hepatoma RH7777 cells2012

    • Author(s)
      Okabe, K., et al
    • Journal Title

      Mol.Carcinog.

      Volume: (印刷中) Issue: 4 Pages: 247-254

    • DOI

      10.1002/mc.21851

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Constitutively active lysophosphatidic acid receptor-1 enhances the induction of matrix metalloproteinase-22012

    • Author(s)
      Kato, K., et al
    • Journal Title

      Biochem.Biophys.Res.Commun.

      Volume: 417 Issue: 2 Pages: 790-793

    • DOI

      10.1016/j.bbrc.2011.12.036

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential function of lysophosphatidic acid receptors in cell proliferation and migration of neuroblastoma cells2012

    • Author(s)
      Hayashi, M., et al
    • Journal Title

      Cancer Lett.

      Volume: 316 Issue: 1 Pages: 91-96

    • DOI

      10.1016/j.canlet.2011.10.030

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of lysophosphatidic acid receptor-3 by 12-Otetradecanoylphorbol-13-acetate stimulates cell migration of rat liver cells2011

    • Author(s)
      Okabe, K., Kato, K., Teranishi, M., Okumura, M., Fukui, R., Mori, T., Fukushima, N. and Tsujiuchi, T
    • Journal Title

      Cancer Lett

      Volume: 309 Pages: 236-242

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Coordinated interactions between actin and microtubules through crosslinkers in neurite retraction induced by lysophosphatidic acid2011

    • Author(s)
      Fukushima, N., Furuta, D. and Tsujiuchi T
    • Journal Title

      Neurochem. Intl

      Volume: 59 Pages: 109-113

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic and Epigenetic Alterations of Lysophosphatidic Acid Receptor Genes in Rodent Tumors by Experimental Models2011

    • Author(s)
      Tsujiuchi, T., et al
    • Journal Title

      Journal of Toxicologic Pathology

      Volume: 24 Issue: 3 Pages: 143-148

    • DOI

      10.1293/tox.24.143

    • NAID

      10030980293

    • ISSN
      0914-9198, 1881-915X
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] No Involvement of Lysophosphatidic Acid Receptor-3 in Cell Migration of Mouse Lung Tumor Cells Stimulated by 12-O-Tetradecanoylphorbol-13-acetate2011

    • Author(s)
      Okumura, M., et al
    • Journal Title

      Journal of Toxicologic Pathology

      Volume: 24 Issue: 3 Pages: 183-186

    • DOI

      10.1293/tox.24.183

    • NAID

      10030980454

    • ISSN
      0914-9198, 1881-915X
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of lysophosphatidic acid receptor-3 by 12-O-tetradecanoyl phorbol-13-acetate stimulates cell migration of rat liver cells2011

    • Author(s)
      Okabe, K., et al
    • Journal Title

      Cancer Lett.

      Volume: 309 Issue: 2 Pages: 236-242

    • DOI

      10.1016/j.canlet.2011.06.020

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coordinated interactions between actin and microtubules through crosslinkers in neurite retraction induced by lysophosphatidic acid2011

    • Author(s)
      Fukushima, N., et al
    • Journal Title

      Neurochem.Intl.

      Volume: 59 Issue: 2 Pages: 109-113

    • DOI

      10.1016/j.neuint.2011.04.020

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of lysophosphatidic acid receptor-5 gene in the acquisition of growth advantage of rat tumor cells2011

    • Author(s)
      Okabe, K., et al
    • Journal Title

      Mol.Carcinog.

      Volume: 50 Issue: 8 Pages: 635-642

    • DOI

      10.1002/mc.20750

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct DNA methylation patterns of lysophosphatidic acid receptor genes during rat hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined diet2011

    • Author(s)
      Okabe, K., et al
    • Journal Title

      Arch.Toxicol.

      Volume: 85 Issue: 10 Pages: 1303-1310

    • DOI

      10.1007/s00204-011-0656-7

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of lysophosphatidic acid receptor-3 enhances cell migration in rat lung tumor cells2011

    • Author(s)
      Hayashi, M., 他7名
    • Journal Title

      Biochem.Biophys.Res.Commun.

      Volume: 405 Pages: 450-454

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lysophosphatidic acid influences initial neuronal polarity establishment2010

    • Author(s)
      Yamane, M., Furuta, D., Fukushima, N.
    • Journal Title

      Neurosci.Lett.

      Volume: 480 Pages: 154-157

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lysophosphatidic acid receptor-3 increases tumorigenicity and aggressiveness of rat hepatoma RH7777 cells

    • Author(s)
      Okabe, K., Hayashi, M., Kato, K., Okumura, M., Fukui, R., Honoki, K., Fukushima, N. and Tsujiuchi, T
    • Journal Title

      Mol. Carcinog

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] Lysophosphatidic acid signaling in neural functions2011

    • Author(s)
      Fukushima, N
    • Organizer
      Molecular targets for treatment of pain
    • Place of Presentation
      近畿大学(東大阪市)
    • Year and Date
      2011-07-19
    • Related Report
      2011 Final Research Report
  • [Presentation] Lysophosphatidic Acid Signaling Is Involved in Neurite Branch Formation2011

    • Author(s)
      Fukushima, N., 他4名
    • Organizer
      The 10th International Conference on AD/PD
    • Place of Presentation
      Barcelona
    • Year and Date
      2011-03-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] Lysophosphatidic acid signaling in neural functions2011

    • Author(s)
      Fukushima, N.
    • Organizer
      Molecular targets for treatment of pain
    • Place of Presentation
      近畿大学薬学部(東大阪市)(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 神経発達とリゾホスファチジン酸シグナル2009

    • Author(s)
      Fukushima Nobuyuki
    • Organizer
      脂質メディエーターワークショップ
    • Place of Presentation
      草津
    • Year and Date
      2009-12-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] Lysophosphatidic acid receptor 3 is involved in neurite branching formation in hippocampal neurons2009

    • Author(s)
      Furuta Daisuke, 他4名
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] LPA induces neurite shape changes through LPA32009

    • Author(s)
      Furuta Daisuke, 他4名
    • Organizer
      4th International Conference on PhospholipaseA2 and Lipid Mediators
    • Place of Presentation
      東京
    • Year and Date
      2009-05-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] Regulation of neurite morphology by LPA2009

    • Author(s)
      Fukushima Nobuyuki
    • Organizer
      4th International Conference on PhospholipaseA2 and Lipid Mediators
    • Place of Presentation
      東京
    • Year and Date
      2009-05-27
    • Related Report
      2009 Annual Research Report
  • [Book] Cytoskeleton of the nervous system. Series : Advances in Neurobiology2011

    • Author(s)
      Fukushima, N.
    • Total Pages
      774
    • Publisher
      Springer
    • Related Report
      2010 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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