Department of Biology, Indiana University, Bloomington, Indiana, United States of America.
PLoS Pathog. 2011 Sep;7(9):e1002201. doi: 10.1371/journal.ppat.1002201. Epub 2011 Sep 1.
Protozoa in the phylum Apicomplexa are a large group of obligate intracellular parasites. Toxoplasma gondii and other apicomplexan parasites, such as Plasmodium falciparum, cause diseases by reiterating their lytic cycle, comprising host cell invasion, parasite replication, and parasite egress. The successful completion of the lytic cycle requires that the parasite senses changes in its environment and switches between the non-motile (for intracellular replication) and motile (for invasion and egress) states appropriately. Although the signaling pathway that regulates the motile state switch is critical to the pathogenesis of the diseases caused by these parasites, it is not well understood. Here we report a previously unknown mechanism of regulating the motility activation in Toxoplasma, mediated by a protein lysine methyltransferase, AKMT (for Apical complex lysine (K) methyltransferase). AKMT depletion greatly inhibits activation of motility, compromises parasite invasion and egress, and thus severely impairs the lytic cycle. Interestingly, AKMT redistributes from the apical complex to the parasite body rapidly in the presence of egress-stimulating signals that increase [Ca²⁺] in the parasite cytoplasm, suggesting that AKMT regulation of parasite motility might be accomplished by the precise temporal control of its localization in response to environmental changes.
顶复门原生动物是一类专性细胞内寄生的大型寄生虫。刚地弓形虫和其他顶复门寄生虫，如恶性疟原虫，通过重复它们的裂解周期来引起疾病，该周期包括宿主细胞入侵、寄生虫复制和寄生虫逸出。裂解周期的成功完成需要寄生虫感知其环境变化，并适当地在非运动（用于细胞内复制）和运动（用于入侵和逸出）状态之间切换。虽然调节运动状态转换的信号通路对这些寄生虫引起的疾病的发病机制至关重要，但它尚未得到很好的理解。在这里，我们报道了一种以前未知的调节刚地弓形虫运动性激活的机制，该机制由一种蛋白赖氨酸甲基转移酶 AKMT（顶复体赖氨酸（K）甲基转移酶）介导。AKMT 耗竭会严重抑制运动性的激活，损害寄生虫的入侵和逸出，从而严重损害裂解周期。有趣的是，在刺激逸出的信号存在下，AKMT 会从顶复体快速重新分布到寄生虫体部，这些信号会增加寄生虫细胞质中的 [Ca²⁺]，这表明 AKMT 对寄生虫运动性的调节可能是通过对其定位的精确时间控制来实现的，以响应环境变化。
