An extracellular redox signal triggers calcium release and impacts the asexual development of Toxoplasma gondii
An extracellular redox signal triggers calcium release and impacts the asexual development of Toxoplasma gondii
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细胞外氧化还原信号触发钙释放并影响弓形虫的无性发育
DOI：
10.1101/2021.02.04.429728
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Alves E
中科院分区：
文献类型：
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作者：
Alves E
生物体感知和响应环境氧化还原波动的能力依赖于一个信号网络，但在顶复门寄生虫如刚地弓形虫中还不完全清楚。氧化还原的变化对这种细胞内寄生虫发育的影响尚不清楚。在这里，我们提供了一个修订后的收集58个基因含有典型的抗氧化功能相关的结构域，其编码的蛋白质广泛分布在不同的细胞隔室。我们证明，向感染T. gondiriggers细胞内寄生虫的胞质溶胶中的Ca2+通量，其可以诱导排出。与现有模型一致，外源性H2O2触发的出口依赖于钙依赖性蛋白激酶3和甘油二酯激酶。最后，我们表明，过表达谷氧还蛋白roGFP 2氧化还原传感器融合蛋白在寄生虫空泡严重影响寄生虫复制。这些数据突出了存在于弓形虫中的丰富的氧化还原网络，证明了细胞外氧化还原和细胞内Ca2+信号传导之间的联系，这种联系可以在寄生虫排出中达到高潮。我们的研究结果还表明，细胞内环境的氧化还原电位有助于正常的寄生虫生长。结合起来，我们的研究结果突出了氧化还原作为寄生虫生物学的未开发调节剂的重要作用。
The ability of an organism to sense and respond to environmental redox fluctuations relies on a signaling network that is incompletely understood in apicomplexan parasites such asToxoplasma gondii. The impact of changes in redox upon the development of this intracellular parasite is not known. Here, we provide a revised collection of 58 genes containing domains related to canonical antioxidant function, with their encoded proteins widely dispersed throughout different cellular compartments. We demonstrate that addition of exogenous H2O2to human fibroblasts infected withT. gondiitriggers a Ca2+flux in the cytosol of intracellular parasites that can induce egress. In line with existing models, egress triggered by exogenous H2O2is reliant upon both Calcium-Dependent Protein Kinase 3 and diacylglycerol kinases. Finally, we show that the overexpression a glutaredoxin-roGFP2 redox sensor fusion protein in the parasitophorous vacuole severely impacts parasite replication. These data highlight the rich redox network that exists inT. gondii, evidencing a link between extracellular redox and intracellular Ca2+signaling that can culminate in parasite egress. Our findings also indicate that the redox potential of the intracellular environment contributes to normal parasite growth. Combined, our findings highlight the important role of redox as an unexplored regulator of parasite biology.