Lysophosphatidic acid induces neuronal shape changes via a novel, receptor-mediated signaling pathway: similarity to thrombin action (original) (raw)
Abstrad Lysophosphatidic acid (LPA) is a mitogenic phospholipid produced by certain adivated cells and present in serum. LPA stimulates phospholipase C and inhibits adenylate cyclase in its target cells, apparently by adivating a specific G-protein-coupled receptor. Here, we demonstrate that LPA causes transient rounding of N1E-115 and NG1O8-15 neuronal cells accompanied by growth cone collapse and retradion of neurites. The effed of LPA is concentration dependent, being half-maximal at 10-20 nr i, 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-adivating peptide (TRP) (K. Jalink and W. H. Moolenaar, J. Cell Biol., 118: 411-419, 1992); yet, LPA and thrombin appear to ad through distind receptors. LPA-induced shape changes, like those induced by thrombin and TRP, are driven by contradion of the cortical adin 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 adivity. Treatment of cells with pervanadate seledively inhibits LPA-and TRP-induced shape changes as well as pGOsrcadivation.
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