The spinster homolog, two of hearts, is required for sphingosine 1-phosphate signaling in zebrafish.
The spinster homolog, two of hearts, is required for sphingosine 1-phosphate signaling in zebrafish.
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DOI：
10.1016/j.cub.2008.10.061
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发表时间：
2008-12-09
期刊：
影响因子：
--
通讯作者：
Stainier DY
中科院分区：
文献类型：
--
作者：
Osborne N;Brand-Arzamendi K;Ober EA;Jin SW;Verkade H;Holtzman NG;Yelon D;Stainier DY
生物活性脂质鞘氨醇1-磷酸（S1P）及其G蛋白偶联受体在心血管、免疫和神经发育和功能中起重要作用。尽管它很重要，但关于S1P信号仍然存在许多问题，包括细胞内合成的S1P如何从细胞中释放出来。斑马鱼编码S1P受体Mil /S1P2基因的突变破坏了原始心管的形成。我们发现斑马鱼的另一个基因座，两个心脏（toh）的突变导致的表型在形态学上与mil/s1p2突变体中所见的表型没有区别。对toh的定位克隆表明，它编码了一个假定的跨膜转运蛋白的Spinster-like家族成员。这些蛋白质的生物学功能尚不清楚，尽管果蝇和斑马鱼没有真正开始突变的表型表明这些蛋白质可能在脂质运输中发挥作用。通过功能增益和功能损失分析，我们发现toh是S1P2信号传递所必需的。进一步的证据表明，Toh参与了S1P的贩运或手机释放。
The bioactive lipid sphingosine 1-phosphate (S1P) and its G protein-coupled receptors play critical roles in cardiovascular, immune and neural development and function. Despite its importance, many questions remain about S1P signaling, including how S1P, which is synthesized intracellularly, is released from cells. Mutations in the zebrafish gene encoding the S1P receptor Miles Apart (Mil)/S1P2 disrupt the formation of the primitive heart tube. We find that mutations of another zebrafish locus, two of hearts (toh), cause phenotypes that are morphologically indistinguishable from those seen in mil/s1p2 mutants. Positional cloning of toh reveals that it encodes a member of the Spinster-like family of putative transmembrane transporters. The biological functions of these proteins are poorly understood, although phenotypes of the Drosophila spinster and zebrafish not really started mutants suggest that these proteins may play a role in lipid trafficking. Through gain- and loss-of-function analyses, we show that toh is required for signaling by S1P2. Further evidence indicates that Toh is involved in the trafficking or cellular release of S1P.
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影响因子：
10.8
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1073/pnas.0603734103
发表时间：
2006-10-31
影响因子：
11.1
作者：
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通讯作者：
Spiegel, Sarah