ABSTRACT
Sphingosine 1-phosphate(S1P),a bioactive lipid signaling molecule,plays important roles in diverse cellular functions such as cell proliferation,differentiation and migration,etc. S1P is intracellularly produced from sphingosine and subse?quently released to the extracellular fluid,then specifically binds to S1P receptors on target cells. S1P mainly originates from hemato?poietic cells and vascular endothelial cells. Several findings have revealed that ATP-binding cassette(ABC)transporters in erythro?cytes and platelets and Spinster homologue 2(Spns2)in endothelial cells both function as S1P transporters. Spns2 is proposed to be the first physiologically functional S1P transporter. Based on the amino acid sequence homology,Spns2 is predicted to belong to the major facilitator superfamily(MFS)transporters. Spns2-deficient mice are recently used for the further characterization of Spns2 func?tion. Accumulating results suggest that the S1P concentration in the plasma of Spns2-deficient mice is reduced notably compared with wild-type mice. In addition,lymphocyte egress to the blood stream in Spns2-deficient mice is blocked. Here,we review the research history,enzymatic properties,substrate,physiological functions of Spns2 and the correlation between Spns2 and diseases such as au?toimmune diseases and cancer,which could provide fundamental reference for further study of Spns2.
ABSTRACT
Sphingosine 1-phosphate (S1P), a bioactive lipid signaling molecule, plays important roles in diverse cellular functions such as cell proliferation, differentiation and migration, etc. S1P is intracellularly produced from sphingosine and subsequently released to the extracellular fluid, then specifically binds to S1P receptors on target cells. S1P mainly originates from hematopoietic cells and vascular endothelial cells. Several findings have revealed that ATP-binding cassette (ABC) transporters in erythrocytes and platelets and Spinster homologue 2 (Spns2) in endothelial cells both function as S1P transporters. Spns2 is proposed to be the first physiologically functional S1P transporter. Based on the amino acid sequence homology, Spns2 is predicted to belong to the major facilitator superfamily (MFS) transporters. Spns2-deficient mice are recently used for the further characterization of Spns2 function. Accumulating results suggest that the S1P concentration in the plasma of Spns2-deficient mice is reduced notably compared with wild-type mice. In addition, lymphocyte egress to the blood stream in Spns2-deficient mice is blocked. Here, we review the research history, enzymatic properties, substrate, physiological functions of Spns2 and the correlation between Spns2 and diseases such as autoimmune diseases and cancer, which could provide fundamental reference for further study of Spns2.