The Unfolded Protein Response in the Protozoan Parasite Toxoplasma gondii Features Translational and Transcriptional Control
The Unfolded Protein Response in the Protozoan Parasite Toxoplasma gondii Features Translational and Transcriptional Control
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DOI：
10.1128/ec.00021-13
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发表时间：
2013-07-01
期刊：
影响因子：
--
通讯作者：
Sullivan, William J., Jr.
中科院分区：
文献类型：
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作者：
Joyce, Bradley R.;Tampaki, Zoi;Sullivan, William J., Jr.
未折叠蛋白反应（unfolded protein response，UPR）是内质网（endoplasmic reticulum，ER）中蛋白质稳态受到干扰时的一个重要调控网络。在哺乳动物细胞中，UPR以旨在恢复蛋白质稳定控制的基因表达的翻译和转录机制为特征。UPR的一个核心特征是PERK（EIF 2AK 3/PEK）对真核起始因子-2（eIF 2）的α亚基进行磷酸化，这通过降低整体蛋白质合成来减少新生蛋白质流入ER，同时优先翻译关键转录激活因子的基因，其功能是扩大该分泌细胞器的加工能力。在ER应激时，已知顶复门寄生虫刚地弓形虫诱导弓形虫eIF 2 α的磷酸化和较低的翻译起始。为了表征这种寄生虫中随后的UPR的性质，我们进行了微阵列分析，以测量ER应激期间转录组和翻译控制的变化。我们确定，一个集合的转录本与分泌过程中诱导响应ER应激，支持的想法，即在弓形虫的UPR的转录诱导阶段发生。此外，我们确定，约500个基因转录增强关联翻译核糖体在内质网应激。这些靶基因中的许多被认为参与基因表达，包括JmjC 5，其在ER应激期间继续被积极翻译。这项研究表明，弓形虫触发UPR在ER应力，翻译和转录调控机制的功能，这可能是重要的寄生虫的入侵和发展。
The unfolded protein response (UPR) is an important regulatory network that responds to perturbations in protein homeostasis in the endoplasmic reticulum (ER). In mammalian cells, the UPR features translational and transcriptional mechanisms of gene expression aimed at restoring proteostatic control. A central feature of the UPR is phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF2) by PERK (EIF2AK3/PEK), which reduces the influx of nascent proteins into the ER by lowering global protein synthesis, coincident with preferential translation of key transcription activators of genes that function to expand the processing capacity of this secretory organelle. Upon ER stress, the apicomplexan parasite Toxoplasma gondii is known to induce phosphorylation of Toxoplasma eIF2 alpha and lower translation initiation. To characterize the nature of the ensuing UPR in this parasite, we carried out microarray analyses to measure the changes in the transcriptome and in translational control during ER stress. We determined that a collection of transcripts linked with the secretory process are induced in response to ER stress, supporting the idea that a transcriptional induction phase of the UPR occurs in Toxoplasma. Furthermore, we determined that about 500 gene transcripts showed enhanced association with translating ribosomes during ER stress. Many of these target genes are suggested to be involved in gene expression, including JmjC5, which continues to be actively translated during ER stress. This study indicates that Toxoplasma triggers a UPR during ER stress that features both translational and transcriptional regulatory mechanisms, which is likely to be important for parasite invasion and development.