细胞内运输。在ORP5和ORP8介导的内质网-质膜接触位点处的PI4P/磷脂酰丝氨酸反向转运
INTRACELLULAR TRANSPORT. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts.
作者信息
Chung Jeeyun, Torta Federico, Masai Kaori, Lucast Louise, Czapla Heather, Tanner Lukas B, Narayanaswamy Pradeep, Wenk Markus R, Nakatsu Fubito, De Camilli Pietro
机构信息
Department of Cell Biology, Howard Hughes Medical Institute, Kavli Institute for Neuroscience, and Program for Cellular Neuroscience, Neurodegeneration, and Repair, Yale School of Medicine, New Haven, CT 06520, USA.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117456 Singapore.
出版信息
Science. 2015 Jul 24;349(6246):428-32. doi: 10.1126/science.aab1370.
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 countertransport 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.
在内质网（ER）与其他膜的接触位点，细胞膜双层之间的脂质转移有助于维持膜脂质稳态。我们发现，两种相似的ER整合膜蛋白，即氧甾醇结合蛋白（OSBP）相关蛋白5（ORP5）和ORP8，通过其普列克底物蛋白同源结构域与该膜中的磷脂酰肌醇4-磷酸（PI4P）相互作用，将ER与质膜（PM）相连。它们的OSBP相关结构域（ORDs）含有PI4P或磷脂酰丝氨酸（PS），并在双层之间交换这些脂质。功能获得和功能丧失实验表明，ORP5和ORP8可介导ER与PM之间的PI4P/PS反向转运，从而将PI4P递送至ER定位的PI4P磷酸酶Sac1进行降解，并将PS从ER转运至PM。这种交换有助于控制质膜PI4P水平，并在PM中选择性富集PS。
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