An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell
An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell
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DOI：
10.7554/elife.10809
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发表时间：
2015-11-18
期刊：
影响因子：
7.7
通讯作者：
Tonkin, Christopher J.
中科院分区：
文献类型：
--
作者：
Coffey, Michael J.;Sleebs, Brad E.;Tonkin, Christopher J.
弓形虫感染导致宿主细胞发生巨大变化。在这里，我们确定了一种新的宿主细胞效应器输出途径，需要高尔基体驻留的乙酰基蛋白酶5（ASP 5）。我们证明，ASP 5切割高度限制的氨基酸基序，具有相似性的PEXEL基序的疟原虫寄生虫。我们表明，ASP 5成熟的基板在N-和C-末端的蛋白质，也控制贩运的效应没有这个主题。此外，ASP 5控制纳米管网络的建立，并且是将宿主线粒体有效募集到液泡所需的。对宿主基因表达的评估表明，ASP 5依赖性途径影响弓形虫赋予其宿主细胞的数千种转录变化。所有这些变化导致Delta asp 5速殖子在体内的毒力减弱。这项工作的特点是第一个确定的机器所需的出口弓形虫效应到受感染的宿主细胞。
Infection by Toxoplasma gondii leads to massive changes to the host cell. Here, we identify a novel host cell effector export pathway that requires the Golgi-resident aspartyl protease 5 (ASP5). We demonstrate that ASP5 cleaves a highly constrained amino acid motif that has similarity to the PEXEL-motif of Plasmodium parasites. We show that ASP5 matures substrates at both the N- and C-terminal ends of proteins and also controls trafficking of effectors without this motif. Furthermore, ASP5 controls establishment of the nanotubular network and is required for the efficient recruitment of host mitochondria to the vacuole. Assessment of host gene expression reveals that the ASP5-dependent pathway influences thousands of the transcriptional changes that Toxoplasma imparts on its host cell. All these changes result in attenuation of virulence of Delta asp5 tachyzoites in vivo. This work characterizes the first identified machinery required for export of Toxoplasma effectors into the infected host cell.