16 research outputs found
Mouse SPNS2 Functions as a Sphingosine-1-Phosphate Transporter in Vascular Endothelial Cells
Sphingosine-1-phosphate (S1P), a sphingolipid metabolite that is produced inside
the cells, regulates a variety of physiological and pathological responses via
S1P receptors (S1P1–5). Signal transduction between cells consists of
three steps; the synthesis of signaling molecules, their export to the
extracellular space and their recognition by receptors. An S1P concentration
gradient is essential for the migration of various cell types that express S1P
receptors, such as lymphocytes, pre-osteoclasts, cancer cells and endothelial
cells. To maintain this concentration gradient, plasma S1P concentration must be
at a higher level. However, little is known about the molecular mechanism by
which S1P is supplied to extracellular environments such as blood plasma. Here,
we show that SPNS2 functions as an S1P transporter in vascular endothelial cells
but not in erythrocytes and platelets. Moreover, the plasma S1P concentration of
SPNS2-deficient mice was reduced to approximately 60% of wild-type, and
SPNS2-deficient mice were lymphopenic. Our results demonstrate that SPNS2 is the
first physiological S1P transporter in mammals and is a key determinant of
lymphocyte egress from the thymus