Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cell Microbiol. 2015 Nov;17(11):1618-39. doi: 10.1111/cmi.12460. Epub 2015 Jul 7.
Apicomplexans are a diverse group of obligate parasites occupying different intracellular niches that require modification to meet the needs of the parasite. To efficiently manipulate their environment, apicomplexans translocate numerous parasite proteins into the host cell. Whereas some parasites remain contained within a parasitophorous vacuole membrane (PVM) throughout their developmental cycle, others do not, a difference that affects the machinery needed for protein export. A signal-mediated pathway for protein export into the host cell has been characterized in Plasmodium parasites, which maintain the PVM. Here, we functionally demonstrate an analogous host-targeting pathway involving organellar staging prior to secretion in the related bovine parasite, Babesia bovis, a parasite that destroys the PVM shortly after invasion. Taking into account recent identification of a similar signal-mediated pathway in the coccidian parasite Toxoplasma gondii, we suggest a model in which this conserved pathway has evolved in multiple steps from signal-mediated trafficking to specific secretory organelles for controlled secretion to a complex protein translocation process across the PVM.
顶复门生物是一类多样化的专性寄生虫，占据不同的细胞内小生境，需要进行修饰以满足寄生虫的需求。为了有效地操纵其环境，顶复门生物将许多寄生虫蛋白转运到宿主细胞中。虽然有些寄生虫在整个发育周期中仍被局限在寄生泡膜（PVM）内，但其他寄生虫则不然，这种差异影响了蛋白输出所需的机制。在维持 PVM 的疟原虫中，已经对蛋白向宿主细胞输出的信号介导途径进行了特征描述。在这里，我们在相关的牛源寄生虫巴贝斯虫中进行了功能验证，该寄生虫在入侵后不久就破坏了 PVM，在分泌前涉及细胞器分期的类似宿主靶向途径。考虑到最近在肉孢子虫寄生虫弓形虫中鉴定出类似的信号介导途径，我们提出了一个模型，其中这个保守途径通过信号介导的运输进化为多个步骤，从特定分泌细胞器的受控分泌到 PVM 上的复杂蛋白转运过程。
