Lipid rafts as platforms for sphingosine 1-phosphate metabolism and signalling

Spontaneous segregation of cholesterol and sphingolipids as a liquid-ordered phase leads to their clustering in selected membrane areas, the lipid rafts. These specialized membrane domains enriched in gangliosides, sphingomyelin, cholesterol and selected proteins involved in signal transduction, organize and determine the function of multiprotein complexes involved in several aspects of signal transduction, thus regulating cell homeostasis. Sphingosine 1-phosphate, an important biologically active mediator, is involved in several signal transduction processes regulating a plethora of cell functions and, not only several of its downstream effectors tend to localize in lipid rafts, some of the enzymes involved in its pathway, of receptors involved in its signalling and its transporters have been often found in these membrane microdomains. Considering this, in this review we address what is currently known regarding the relationship between sphingosine 1-phosphate metabolism and signalling and plasma membrane lipid rafts. •Association of sphingosine kinase 1 to lipid rafts is essential for its activity.•Membrane localization of LPPs makes them essential to regulate extracellular S1P.•ABC transporters not only export S1P, they are also regulated by S1P signalling.•S1P1 recruited to caveolin-rich domains is required for endothelial barrier function.•S1P receptors can cross-talk actively cross-talk with other receptor systems.