Sphingolipids are key structural components of membranes, but are also important signalling molecules, regulating both cell survival and migration. Sphingosine 1-phosphate (S1P) and sphingosylphosphorylcholine (SPC) in particular have been implicated in migration and metastasis in cancer cells. Vimentin is an intermediate filament protein with well-known functions in cell migration, but little is known about the relationship between vimentin and signalling through S1P or SPC. Here (p. 2057), John Eriksson, Kid Törnquist and colleagues identify a novel sphingolipid–vimentin signalling pathway that is involved in the regulation of cell migration. They observed that both S1P and SPC inhibited chemotaxis, as well as the wound-healing ability of MDA-MB-435S and C643 cells. Treatment with sphingolipids also decreased the turnover of vimentin filament precursors and reorganised the vimentin filament network. Using mass spectrometry, the authors found that vimentin was phosphorylated at serine (S)71 within 10 minutes of the application of sphingolipids. They also demonstrated that the effects of sphingolipids on cell migration were mediated by the S1P₂ receptor and ROCK kinase, as both were necessary for vimentin phosphorylation. Finally, using vimentin-knockout mouse embryonic fibroblasts, as well as a phosphorylation-resistant vimentin mutant, the authors showed that sphingolipids could not inhibit cell migration without the phosphorylation of vimentin. Therefore, this study demonstrates that S1P and SPC sphingolipids act through the S1P₂ receptor and ROCK kinase to phosphorylate vimentin at S71, thus inhibiting cell migration.

• © 2015. Published by The Company of Biologists Ltd