Toxoplasma gondii glutathione S-transferase 2 plays an important role in partial secretory protein transport
Toxoplasma gondii glutathione S-transferase 2 plays an important role in partial secretory protein transport
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弓形虫谷胱甘肽S-转移酶2在部分分泌蛋白转运中发挥重要作用
DOI：
10.1096/fj.202001987rr
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发表时间：
2021-02-01
期刊：
影响因子：
4.8
通讯作者：
Liu, Qun
中科院分区：
文献类型：
--
作者：
Li, Shuang;Liu, Jing;Liu, Qun
弓形虫是一种顶复体寄生虫，具有三种独特的分泌细胞器：微丝、棒状体和致密颗粒。几乎所有的分泌蛋白都通过内质网（ER）和高尔基体系统转运，通过精确的靶向和包装在各自的目的地发挥作用。谷胱甘肽S-转移酶（GST）是一种超基因家族酶，具有多种功能，包括调节细胞增殖和死亡信号通路，参与哺乳动物细胞的运输和代谢。然而，GST在弓形虫中的作用尚未得到解释。在这项研究中，我们确定了三个GST蛋白在弓形虫，其中GST 2作为一个膜蛋白，定位到高尔基体-内体系统和共定位的蛋白质参与囊泡运输，以及，包括小突触泡蛋白，推定分拣蛋白（VPS 10），Rab 5和Rab 6，作为囊泡运输因子的功能。此外，TgGST 2的缺失导致Rab 5和Rab 6分布的离散点，和不正确的定位和几种分泌蛋白的表达降低，并显着降低侵袭能力和对小鼠的毒力。与其与囊泡转运蛋白的关系一致，TgGST 2的分布依赖于高尔基体后的运输。总体而言，我们的研究结果表明，TgGST 2有助于囊泡运输，并在寄生虫裂解周期中发挥关键作用。
Toxoplasma gondii is an apicomplexan parasite, which has three unique secretory organelles: micronemes, rhoptries, and dense granules. Almost all the secreted proteins are transported through the endoplasmic reticulum (ER) and Golgi system to function in their respective destination by accurate targeting and packaging. Glutathione S-transferase (GST) is a supergene family enzyme that has multiple functions, which include regulation of cell proliferation and death signaling pathways, and participation in transportation and metabolism in mammal cells. However, the role of GST in Toxoplasma gondii has not been explained. In this study, we identified three GST proteins in T gondii, of which GST2 acts as a membrane protein that localizes to the Golgi-endosomal system and colocalizes with proteins involved in vesicle transport as well, including synaptobrevin, putative sortilin (VPS10), Rab5 and Rab6, which function as vesicle transport factors. Moreover, the loss of TgGST2 leads to Rab5 and Rab6 distribution of discrete puncta, and incorrect localization and decreased expression of several secretory proteins, and to significantly reduced invasion capacity and virulence to mice. Consistent with its relation to vesicle transport proteins, the distribution of TgGST2 relies on post-Golgi trafficking. Overall, our findings demonstrated that TgGST2 contributes to vesicle trafficking and plays a critical role in parasite lytic cycle.