鞘氨醇-1-磷酸转运体Spns2的研究进展

Spns 2,a transporter of sphingosine-1-phosphate:research advances

鞘氨醇-1-磷酸(S1P)是一种鞘脂类信号分子,在细胞增殖、分化和迁移等诸多方面发挥重要的调节作用。S1P在细胞内生成,随后释放到细胞外与靶细胞膜上的S1PR受体结合。S1P的体内来源主要是造血细胞和血管内皮细胞。造血细胞中S1P的释放主要通过ABC转运蛋白家族,而血管内皮细胞中S1P的释放则是通过Spns2。Spns2是首个被发现并确认具有重要生理功能的S1P转运蛋白,属于主要协助转运蛋白超家族。应用Spns2基因敲除小鼠模型研究发现Spns2缺陷小鼠的血浆S1P水平较野生小鼠明显下降,淋巴细胞外迁受到抑制。本文将对Spns2的研究历史、结构特性、作用底物、生理功能,以及Spns2与免疫性疾病和癌症的相关性进行简要介绍,为进一步研究Spns2提供重要参考。

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.