Oxysterol binding protein (OSBP) extracts cholesterol from the ER to deliver it to the TGN via counter exchange and subsequent hydrolysis of the phosphoinositide PI(4)P. Here, we show that this pathway is essential in polarized epithelial cells where it contributes not only to the proper subcellular distribution of cholesterol but also to the trans-Golgi sorting and trafficking of numerous plasma membrane cargo proteins with apical or basolateral localization. Reducing the expression of OSBP, blocking its activity, or inhibiting a PI4Kinase that fuels OSBP with PI(4)P abolishes the epithelial phenotype. Waves of cargo enrichment in the TGN in phase with OSBP and PI(4)P dynamics suggest that OSBP promotes the formation of lipid gradients along the TGN, which helps cargo sorting. During their transient passage through the trans-Golgi, polarized plasma membrane proteins get close to OSBP but fail to be sorted when OSBP is silenced. Thus, OSBP lipid exchange activity is decisive for polarized cargo sorting and distribution in epithelial cells.

中文翻译：

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ER-跨高尔基体接触位点的脂质交换控制极化货物分类


氧甾醇结合蛋白 (OSBP) 从 ER 中提取胆固醇，通过反向交换和随后磷酸肌醇 PI(4)P 的水解将其输送至 TGN。在这里，我们表明该途径在极化上皮细胞中至关重要，它不仅有助于胆固醇的正确亚细胞分布，而且有助于大量具有顶端或基底外侧定位的质膜货物蛋白的跨高尔基体分选和运输。减少 OSBP 的表达、阻断其活性或抑制用 PI(4)P 为 OSBP 提供能量的 PI4 激酶可消除上皮表型。 TGN 中的货物富集波与 OSBP 和 PI(4)P 动力学同步表明 OSBP 促进了沿 TGN 的脂质梯度的形成，这有助于货物分选。在短暂穿过高尔基体期间，极化质膜蛋白会接近 OSBP，但当 OSBP 沉默时无法进行分选。因此，OSBP 脂质交换活性对于上皮细胞中的极化货物分选和分布具有决定性作用。