Spillman Natalie J, Beck Josh R, Ganesan Suresh M, Niles Jacquin C, Goldberg Daniel E
Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, 63110, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA.
Cell Microbiol. 2017 Jun;19(6). doi: 10.1111/cmi.12719. Epub 2017 Jan 24.
The malaria parasite exports numerous proteins into its host red blood cell (RBC). The trafficking of these exported effectors is complex. Proteins are first routed through the secretory system, into the parasitophorous vacuole (PV), a membranous compartment enclosing the parasite. Proteins are then translocated across the PV membrane in a process requiring ATP and unfolding. Once in the RBC compartment the exported proteins are then refolded and further trafficked to their final localizations. Chaperones are important in the unfolding and refolding processes. Recently, it was suggested that the parasite TRiC chaperonin complex is exported, and that it is involved in trafficking of exported effectors. Using a parasite-specific antibody and epitope-tagged transgenic parasites we could observe no export of Plasmodium TRiC into the RBC. We tested the importance of the parasite TRiC by creating a regulatable knockdown line of the TRiC-θ subunit. Loss of the parasite TRiC-θ led to a severe growth defect in asexual development, but did not alter protein export into the RBC. These observations indicate that the TRiC proteins play a critical role in parasite biology, though their function, within the parasite, appears unrelated to protein trafficking in the RBC compartment.
疟原虫会向其宿主红细胞（RBC）输出大量蛋白质。这些输出效应蛋白的运输过程很复杂。蛋白质首先通过分泌系统进入寄生泡（PV），这是一种包围寄生虫的膜性区室。然后蛋白质在一个需要ATP和展开的过程中穿过PV膜。一旦进入红细胞区室，输出的蛋白质就会重新折叠并进一步运输到它们的最终定位点。伴侣蛋白在展开和重新折叠过程中很重要。最近，有人提出寄生虫TRiC伴侣蛋白复合体被输出，并且它参与输出效应蛋白的运输。使用寄生虫特异性抗体和表位标签转基因寄生虫，我们未观察到疟原虫TRiC输出到红细胞中。我们通过创建TRiC-θ亚基的可调节敲低系来测试寄生虫TRiC的重要性。寄生虫TRiC-θ的缺失导致无性发育出现严重生长缺陷，但并未改变蛋白质向红细胞中的输出。这些观察结果表明，TRiC蛋白在寄生虫生物学中起关键作用，尽管它们在寄生虫内的功能似乎与红细胞区室中的蛋白质运输无关。
