Exogenous sphingosine 1-phosphate induces neurite retraction possibly through a cell surface receptor in PC12 cells

Exogenous sphingosine 1-phosphate (S1P), like lysophosphatidic acid (LPA), induced neurite retraction or cell rounding in differentiated PC12 cells. The lysosphingolipid-induced shape change was detected at as low as 1 nM; however, a significant accumulation of intracellular S1P was not detected until 1 microM S1P was applied. Moreover, although exogenous sphingosine caused a significant increase in intracellular S1P by sphingosine kinase-catalyzed phosphorylation, the effect on the shape change was marginal. Exposure of the cells to the immobilized S1P in which the lipid was covalently linked to a glass carrier also resulted in the shape change. These results suggest that the exogenous S1P-induced shape change does not require uptake of the lipid into the cells but possibly requires interaction with a cell surface receptor in the neuronal cells.