Lysophosphatidic acid induces neuronal shape changes via a novel, receptor-mediated signaling pathway: similarity to thrombin action

Cell Growth Differ. 1993 Apr;4(4):247-55.


Lysophosphatidic acid (LPA) is a mitogenic phospholipid produced by certain activated cells and present in serum. LPA stimulates phospholipase C and inhibits adenylate cyclase in its target cells, apparently by activating a specific G-protein-coupled receptor. Here, we demonstrate that LPA causes transient rounding of N1E-115 and NG108-15 neuronal cells accompanied by growth cone collapse and retraction of neurites. The effect of LPA is concentration dependent, being half-maximal at 10-20 nM, and reversibly blocked by suramin, an LPA receptor antagonist. The morphological response to LPA is indistinguishable from that evoked by thrombin or a thrombin receptor-activating peptide (TRP) (K. Jalink and W. H. Moolenaar, J. Cell Biol., 118: 411-419, 1992); yet, LPA and thrombin appear to act through distinct receptors. LPA-induced shape changes, like those induced by thrombin and TRP, are driven by contraction of the cortical actin cytoskeleton and not attributable to prior phospholipid hydrolysis and Ca2+ mobilization nor to other classic second messenger systems. Instead, LPA- and TRP-induced shape changes are accompanied by a small but significant increase in p60src protein tyrosine kinase activity. Treatment of cells with pervanadate selectively inhibits LPA- and TRP-induced shape changes as well as p60src activation. These results indicate that, in N1E-115 and NG108-15 cells, LPA and TRP trigger neurite retraction and cell rounding through a novel, receptor-mediated signaling pathway, and they suggest that p60src may play a role in this pathway.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / physiology
  • Animals
  • Cell Differentiation / drug effects
  • Cell Size / drug effects
  • Cytoskeleton / chemistry
  • Cytoskeleton / physiology
  • Enzyme Activation
  • Lysophospholipids / blood
  • Lysophospholipids / pharmacology*
  • Mice
  • Neurons / cytology
  • Neurons / drug effects*
  • Phenotype
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology
  • Receptors, Thrombin
  • Signal Transduction / drug effects*
  • Thrombin / pharmacology*
  • Tumor Cells, Cultured


  • Actins
  • Lysophospholipids
  • Receptors, Cell Surface
  • Receptors, Thrombin
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins pp60(c-src)
  • Thrombin