Mouse SPNS2 Functions as a Sphingosine-1-Phosphate Transporter in Vascular Endothelial Cells

摘要

Sphingosine-1-phosphate (S1P), a sphingolipid metabolite that is produced insidethe cells, regulates a variety of physiological and pathological responses viaS1P receptors (S1P1–5). Signal transduction between cells consists ofthree steps; the synthesis of signaling molecules, their export to theextracellular space and their recognition by receptors. An S1P concentrationgradient is essential for the migration of various cell types that express S1Preceptors, such as lymphocytes, pre-osteoclasts, cancer cells and endothelialcells. To maintain this concentration gradient, plasma S1P concentration must beat a higher level. However, little is known about the molecular mechanism bywhich S1P is supplied to extracellular environments such as blood plasma. Here,we show that SPNS2 functions as an S1P transporter in vascular endothelial cellsbut not in erythrocytes and platelets. Moreover, the plasma S1P concentration ofSPNS2-deficient mice was reduced to approximately 60% of wild-type, andSPNS2-deficient mice were lymphopenic. Our results demonstrate that SPNS2 is thefirst physiological S1P transporter in mammals and is a key determinant oflymphocyte egress from the thymus.