Analysis of physiological roles of sphingosine-1-phosphate transporter, SPNS2

鞘氨醇-1-磷酸(S1P)是一种生物活性的脂质介质，由细胞内合成、释放并被S1P受体(S1PR1-S1PR5)识别。我们已经鉴定出一种新的S1P转运蛋白SPNS2。为了揭示SPNS2在哺乳动物中的生理作用，我们分析了SPNS2基因敲除(KO)小鼠。S1P大量存在于血浆中，血浆S1P被认为来源于红细胞、活化的血小板和内皮细胞。纯化的SPNS2-KO小鼠血管内皮细胞不能释放S1P，而SPNS2-KO小鼠红细胞和血小板S1P的释放没有变化。这些结果表明，SPNS2是内皮细胞中唯一的S1P转运体。此外，SPNS2-KO小鼠表现出淋巴细胞减少，而胸腺细胞能够分化为成熟细胞并向S1P迁移。这些数据表明，SPNS2在内皮细胞上释放的S1P被成熟胸腺细胞上的S1PR1识别，并使胸腺外流。

Sphingosine-1-phoshphate (S1P), a bioactive lipid mediator, is intracellularly synthesized, released from the cells and recognized by S1P receptors (S1PR1-S1PR5). We had identified a novel S1P transporter, SPNS2. In order to reveal the physiological roles of SPNS2 in mammals, we analyzed SPNS2-knockout (KO) mice.S1P abundantly exists in plasma and plasma S1P is thought to originate from erythrocytes, activated platelets and endothelial cells. Vascular endothelial cells purified from SPNS2-KO mice are unable to release S1P, while S1P release from erythrocytes and platelets of SPNS2-KO mice is not changed. These results suggest that SPNS2 functions as the sole S1P transporter in endothelial cells. Furthermore, SPNS2-KO mice exhibited lymphopenia, while thymocytes are able to differentiate into mature cells and migrate towards S1P. These date indicate that S1P released by SPNS2 on endothelial cells is recognized by S1PR1 on matured thymocytes and enable thymic egress.