Lysophosphatidic acid induces neurite branch formation through LPA3

Mol Cell Neurosci. 2012 May;50(1):21-34. doi: 10.1016/j.mcn.2012.03.006. Epub 2012 Mar 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Lysophospholipids / pharmacology*
  • Mice
  • Neurites / drug effects
  • Neurites / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • PC12 Cells
  • RNA, Small Interfering
  • Rats
  • Receptors, Lysophosphatidic Acid / agonists
  • Receptors, Lysophosphatidic Acid / antagonists & inhibitors
  • Receptors, Lysophosphatidic Acid / metabolism*
  • Tumor Cells, Cultured
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Lysophospholipids
  • RNA, Small Interfering
  • Receptors, Lysophosphatidic Acid
  • Rnd2 protein, mouse
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • rho GTP-Binding Proteins