GPHR is a novel anion channel critical for acidification and functions of the Golgi apparatus
GPHR is a novel anion channel critical for acidification and functions of the Golgi apparatus
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DOI：
10.1038/ncb1773
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发表时间：
2008-10-01
影响因子：
21.3
通讯作者：
Kinoshita, Taroh
中科院分区：
文献类型：
--
作者：
Maeda, Yusuke;Ide, Toru;Kinoshita, Taroh
哺乳动物细胞分泌和内吞途径中的细胞器使管腔酸化，其酸性pH值的调节对于货物蛋白和脂质的运输、加工和糖基化以及细胞器的形态完整性至关重要。细胞器管腔酸化是如何调节的，以及管腔pH值升高是如何扰乱这些基本的细胞过程的，在很大程度上是未知的。在这里，我们描述了一个新的分子参与高尔基酸化。首先，建立了高尔基酸化缺陷突变细胞，表现出蛋白质转运延迟、糖基化受损和高尔基体解体。通过表达克隆，鉴定出一种新的高尔基驻留多跨膜蛋白，称为高尔基pH调节因子（Golgi pH regulator， GPHR），与突变细胞有关。在平面脂质双层中重构后，GPHR表现出电压依赖的阴离子通道活性，可能在反离子电导中起作用。因此，GPHR通过调节酸化来调节高尔基体功能。
The organelles within secretory and endocytotic pathways in mammalian cells have acidified lumens, and regulation of their acidic pH is critical for the trafficking, processing and glycosylation of cargo proteins and lipids, as well as the morphological integrity of the organelles. How organelle lumen acidification is regulated, and how luminal pH elevation disturbs these fundamental cellular processes, is largely unknown. Here, we describe a novel molecule involved in Golgi acidification. First, mutant cells defective in Golgi acidification were established that exhibited delayed protein transport, impaired glycosylation and Golgi disorganization. Using expression cloning, a novel Golgi-resident multi-transmembrane protein, named Golgi pH regulator (GPHR), was identified as being responsible for the mutant cells. After reconstitution in planar lipid bilayers, GPHR exhibited a voltage-dependent anion-channel activity that may function in counterion conductance. Thus, GPHR modulates Golgi functions through regulation of acidification.