Phosphatidylserine transport by ORP/Osh proteins is driven by phosphatidylinositol 4-phosphate
Phosphatidylserine transport by ORP/Osh proteins is driven by phosphatidylinositol 4-phosphate
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DOI：
10.1126/science.aab1346
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发表时间：
2015-07-24
期刊：
影响因子：
56.9
通讯作者：
Drin, Guillaume
中科院分区：
文献类型：
--
作者：
von Filseck, Joachim Moser;Copic, Alenka;Drin, Guillaume
在真核细胞中，磷脂酰丝氨酸（PS）在内质网（ER）中合成，但在质膜（PM）中高度富集，在质膜中它贡献负电荷并特异性募集信号蛋白。这种分布依赖于运输机制，其性质仍然难以捉摸。在这里，我们发现PS转运蛋白Osh 6p提取磷脂酰肌醇4-磷酸（PI 4P），并在两个膜之间将PS交换为PI 4P。我们解决了Osh 6p：PI 4P复合物的晶体结构，并证明了Osh 6p在体内转运PS依赖于PI 4P识别。最后，我们发现，PI 4P-磷酸酶Sac 1 p，通过维持ER/PM界面的PI 4P梯度，驱动PS运输。因此，PS通过氧化固醇结合蛋白相关蛋白（ORP）/氧化固醇结合同源（奥什）蛋白的转运是通过PS/PI 4 P交换循环由PI 4 P代谢提供动力的。
In eukaryotic cells, phosphatidylserine (PS) is synthesized in the endoplasmic reticulum (ER) but is highly enriched in the plasma membrane (PM), where it contributes negative charge and to specific recruitment of signaling proteins. This distribution relies on transport mechanisms whose nature remains elusive. Here, we found that the PS transporter Osh6p extracted phosphatidylinositol 4-phosphate (PI4P) and exchanged PS for PI4P between two membranes. We solved the crystal structure of Osh6p: PI4P complex and demonstrated that the transport of PS by Osh6p depends on PI4P recognition in vivo. Finally, we showed that the PI4P-phosphatase Sac1p, by maintaining a PI4P gradient at the ER/PM interface, drove PS transport. Thus, PS transport by oxysterol-binding protein-related protein (ORP)/oxysterol-binding homology (Osh) proteins is fueled by PI4P metabolism through PS/PI4P exchange cycles.