INTRACELLULAR TRANSPORT. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts.
INTRACELLULAR TRANSPORT. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts.
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DOI：
10.1126/science.aab1370
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发表时间：
2015-07-24
期刊：
影响因子：
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通讯作者：
De Camilli P
中科院分区：
文献类型：
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作者：
Chung J;Torta F;Masai K;Lucast L;Czapla H;Tanner LB;Narayanaswamy P;Wenk MR;Nakatsu F;De Camilli P
内质网(ER)与其他膜接触的细胞膜双层间的脂质转移有助于维持膜脂的动态平衡。我们发现两个相似的内质网完整膜蛋白，氧固醇结合蛋白相关蛋白5(OSBP)相关蛋白5(ORP5)和ORP8，通过它们的pleckstrin同源结构域与质膜上的磷脂酰肌醇4-磷酸(PI4P)相互作用，将内质网连接到质膜(PM)。它们的OSBP相关结构域(ORD)含有PI4P或磷脂酰丝氨酸(PS)，并在双层之间交换这些脂类。功能获得和功能丧失实验表明，ORP5和ORP8可以介导PI4P/PS在ER和PM之间的反向转运，从而将PI4P运送到ER定位的PI4P磷酸酶SAC1进行降解，并将PS从ER运送到PM这种交换有助于控制质膜PI4P水平，并选择性地丰富PM中的PS
Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)–related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP-related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS counter transport between the ER and the PM, thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P levels and selectively enrich PS in the PM.