UMR 5235 CNRS, Université de Montpellier, 34095, Montpellier, France.
Department of Internal Medicine and Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, 1107 2020, Lebanon.
Sci Rep. 2017 Dec 20;7(1):17907. doi: 10.1038/s41598-017-18010-9.
Apicomplexa parasites, including Toxoplasma and Plasmodium species, possess a unique invasion mechanism that involves a tight apposition between the parasite and the host plasma membranes, called "moving junction" (MJ). The MJ is formed by the assembly of the microneme protein AMA1, exposed at the surface of the parasite, and the parasite rhoptry neck (RON) protein RON2, exposed at the surface of the host cell. In the host cell, RON2 is associated with three additional parasite RON proteins, RON4, RON5 and RON8. Here we describe RON4, an additional member of the MJ complex in Toxoplasma. RON4 displays some sequence similarity with RON4 and is cleaved at the C-terminal end before reaching the rhoptry neck. Upon secretion during invasion, RON4 is associated with MJ and targeted to the cytosolic face of the host membrane. We generated a RON4 knock-out cell line and showed that it is not essential for the lytic cycle in vitro, although mutant parasites kill mice less efficiently. Similarly to RON8, RON4 is a coccidian-specific protein and its traffic to the MJ is not affected in absence of RON2, RON4 and RON5, suggesting the co-existence of independent MJ complexes in tachyzoite of Toxoplasma.
Apicomplexa 寄生虫，包括刚地弓形虫和疟原虫等物种，具有独特的入侵机制，涉及寄生虫和宿主质膜之间的紧密贴合，称为“移动连接点”（MJ）。MJ 是由表面暴露的寄生虫微线蛋白 AMA1 和表面暴露的宿主细胞虫体颈蛋白 RON2 组装形成的。在宿主细胞中，RON2 与另外三个寄生虫 RON 蛋白 RON4、RON5 和 RON8 相关联。在这里，我们描述了 Toxoplasma 中 MJ 复合物的另一个成员 RON4。RON4 与 RON4 具有一些序列相似性，并且在到达虫体颈之前在 C 末端被切割。在入侵过程中分泌时，RON4 与 MJ 相关联并靶向宿主膜的细胞质面。我们生成了 RON4 敲除细胞系，并表明它在体外裂解周期中不是必需的，尽管突变寄生虫杀死小鼠的效率较低。与 RON8 类似，RON4 是一种肉孢子虫特异性蛋白，其在 RON2、RON4 和 RON5 缺失的情况下不会影响其向 MJ 的运输，这表明在刚地弓形虫的速殖子中存在独立的 MJ 复合物的共存。
