SPHINGOSINE-1-PHOSPHATE RAPIDLY INDUCES RHO-DEPENDENT NEURITE RETRACTION - ACTION THROUGH A SPECIFIC CELL-SURFACE RECEPTOR

Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid implicat ed in mitogenesis and cytoskeletal remodelling, but its mechanism of a ction is poorly understood. We report here that in N1E-115 neuronal ce lls, S1P mimics the G protein-coupled receptor agonist lysophosphatidi c acid (LPA) in rapidly inducing neurite retraction and soma rounding, a process driven by Rho-dependent contraction of the actin cytoskelet on. S1P is similar to 100-fold more potent than LPA in evoking these s hape changes, with an EC(50) as low as 1.5 nM. Microinjection of S1P h as no effect, neither has addition of sphingosine or ceramide. As with LPA, S1P action is inhibited by suramin and subject to homologous des ensitization; however, the responses to S1P and LPA do not show cross- desensitization. We conclude that S1P activates its own high affinity receptor to trigger Rho-regulated cytoskeletal events. Thus, S1P and L PA may belong to an emerging family of bioactive lysophospholipids tha t act through distinct G protein-coupled receptors to mediate similar actions.