GPR107, a G-protein-coupled Receptor Essential for Intoxication by Pseudomonas aeruginosa Exotoxin A, Localizes to the Golgi and Is Cleaved by Furin
GPR107, a G-protein-coupled Receptor Essential for Intoxication by Pseudomonas aeruginosa Exotoxin A, Localizes to the Golgi and Is Cleaved by Furin
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DOI：
10.1074/jbc.m114.589275
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发表时间：
2014-08-29
影响因子：
4.8
通讯作者：
Ploegh, Hidde L.
中科院分区：
文献类型：
--
作者：
Tafesse, Fikadu G.;Guimaraes, Carla P.;Ploegh, Hidde L.
背景：细菌毒素，包括铜绿假单胞菌外毒素A（PE），是解剖生物过程的有价值的工具。结果：全基因组遗传筛选确定了PE使用的几个新的宿主因子，包括GPR 107。结论：细菌毒素可以帮助鉴定参与细胞内转运关键步骤的新型宿主成分。重要性：GPR 107可能是高尔基体上G蛋白的受体，调节细胞膜转运，包括铜绿假单胞菌外毒素A（PE）在内的许多毒素通过抑制蛋白质合成而杀伤细胞。PE通过翻译延伸因子2的ADP-核糖基化杀死，但许多进入、膜转位和细胞内转运所需的宿主因子仍有待阐明。在人类KBM 7细胞中进行了全基因组遗传筛选，以揭示PE使用的宿主因子，其中几个因子在不同细胞类型中通过CRISPR/Cas9基因编辑得到证实。发现了几种以前未参与PE中毒途径的蛋白质，包括GPR 107，一种孤儿G蛋白偶联受体。GPR 107定位于trans-Golgi网络，是逆行运输所必需的。它被内切蛋白酶弗林蛋白酶切割，二硫键连接两个切割片段。破坏这种关联会影响GPR 107的功能。GPR 107的N-末端区域对其生物学功能至关重要。GPR 107可能是一种长期寻找的与G蛋白相关的调节胞内囊泡转运的受体。
Background: Bacterial toxins, including P. aeruginosa exotoxin A (PE), are valuable tools to dissect biological processes. Results: A genome-wide genetic screen identifies several novel host factors used by PE, including GPR107. Conclusion: Bacterial toxins can help identify novel host components involved in key intracellular trafficking steps. Significance: GPR107 may be a receptor that associates with G-proteins at the Golgi to regulate membrane transport.A number of toxins, including exotoxin A (PE) of Pseudomonas aeruginosa, kill cells by inhibiting protein synthesis. PE kills by ADP-ribosylation of the translation elongation factor 2, but many of the host factors required for entry, membrane translocation, and intracellular transport remain to be elucidated. A genome-wide genetic screen in human KBM7 cells was performed to uncover host factors used by PE, several of which were confirmed by CRISPR/Cas9-gene editing in a different cell type. Several proteins not previously implicated in the PE intoxication pathway were identified, including GPR107, an orphan G-protein-coupled receptor. GPR107 localizes to the trans-Golgi network and is essential for retrograde transport. It is cleaved by the endoprotease furin, and a disulfide bond connects the two cleaved fragments. Compromising this association affects the function of GPR107. The N-terminal region of GPR107 is critical for its biological function. GPR107 might be one of the long-sought receptors that associates with G-proteins to regulate intracellular vesicular transport.