Kawahara Atsuo, Nishi Tsuyoshi, Hisano Yu, Fukui Hajime, Yamaguchi Akihito, Mochizuki Naoki
Department of Structural Analysis, National Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan.
Science. 2009 Jan 23;323(5913):524-7. doi: 10.1126/science.1167449. Epub 2008 Dec 11.
Sphingosine-1-phosphate (S1P) is a secreted lipid mediator that functions in vascular development; however, it remains unclear how S1P secretion is regulated during embryogenesis. We identified a zebrafish mutant, ko157, that displays cardia bifida (two hearts) resembling that in the S1P receptor-2 mutant. A migration defect of myocardial precursors in the ko157 mutant is due to a mutation in a multipass transmembrane protein, Spns2, and can be rescued by S1P injection. We show that the export of S1P from cells requires Spns2. spns2 is expressed in the extraembryonic tissue yolk syncytial layer (YSL), and the introduction of spns2 mRNA in the YSL restored the cardiac defect in the ko157 mutant. Thus, Spns2 in the YSL functions as a S1P transporter in S1P secretion, thereby regulating myocardial precursor migration.
鞘氨醇-1-磷酸（S1P）是一种分泌性脂质介质，在血管发育中发挥作用；然而，在胚胎发生过程中S1P的分泌是如何调节的仍不清楚。我们鉴定出一种斑马鱼突变体ko157，它表现出与S1P受体-2突变体相似的心脏分裂（两个心脏）。ko157突变体中心肌前体细胞的迁移缺陷是由于一种多次跨膜蛋白Spns2的突变引起的，并且可以通过注射S1P来挽救。我们表明，S1P从细胞中的输出需要Spns2。spns2在胚外组织卵黄合胞体层（YSL）中表达，并且在YSL中引入spns2 mRNA可恢复ko157突变体中的心脏缺陷。因此，YSL中的Spns2在S1P分泌中作为S1P转运体发挥作用，从而调节心肌前体细胞的迁移。
