Molecular mechanisms for LPA_3-mediated neurite branch formation

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590109
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kinki 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
• Keywords: リゾホスファチジン酸 / G蛋白質 / 神経軸索 / 分岐

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.

Research Products

• [Journal Article] Lysophosphatidic acid induces neurite branch formation through LPA_3 (2012)
  • Author(s): Furuta, D., Yamane, M., Tsujiuchi, T., Moriyama, R. and Fukushima, N
  • Journal Title: Mol. Cell. Neurosci Volume: 50 Pages: 21-34
  • Peer Reviewed
• [Journal Article] Differential function of lysophosphatidic acid receptors in cell proliferation and migration of neuroblastoma cells (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Induction of lysophosphatidic acid receptor-3 by 12-Otetradecanoylphorbol-13-acetate stimulates cell migration of rat liver cells (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Coordinated interactions between actin and microtubules through crosslinkers in neurite retraction induced by lysophosphatidic acid (2011)
  • Author(s): Fukushima, N., Furuta, D. and Tsujiuchi T
  • Journal Title: Neurochem. Intl Volume: 59 Pages: 109-113
  • 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)
  • Peer Reviewed
• [Presentation] Lysophosphatidic acid signaling in neural functions (2011)
  • 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