Distinct effects on the secretion of MTRAP and AMA1 in Plasmodium yoelii following deletion of acylated pleckstrin homology domain-containing protein
Distinct effects on the secretion of MTRAP and AMA1 in Plasmodium yoelii following deletion of acylated pleckstrin homology domain-containing protein
复制标题
删除酰化普莱克斯特林同源结构域蛋白后对约氏疟原虫中 MTRAP 和 AMA1 分泌的显着影响
DOI：
10.1016/j.parint.2021.102479
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发表时间：
2022
影响因子：
1.9
通讯作者：
Osamu Kaneko
中科院分区：
文献类型：
--
作者：
Nattawat Chaiyawong;Takahiro Ishizaki;Hassan Hakimi;Masahito Asada;Kazuhide Yahata;Osamu Kaneko
疟原虫是疟疾的病原体，是专性细胞内生物。在人类中，发病机制是由血液阶段寄生虫引起的，它在红细胞内繁殖，因此红细胞侵入是一个重要的发育步骤。裂殖子形式的寄生虫释放到血流中协调地从微丝分泌细胞器分泌一组蛋白质，用于滑行运动、与靶幼稚红细胞建立紧密连接以及随后的内化。在刚地弓形虫中鉴定的一种蛋白质促进微线体与质膜融合以用于胞吐作用;即，含酰化普列克底物蛋白同源结构域的蛋白质（APH）。为了深入了解疟疾寄生虫的差异微线放电，在这项研究中，我们分析了APH缺失的后果，在啮齿类动物疟疾模型，约氏疟原虫，使用DiCre为基础的诱导敲除方法。我们发现APH缺失导致寄生虫无性生长和红细胞侵袭减少，一些寄生虫保留了在没有APH的情况下侵袭和生长的能力。APH缺失损害了微线体蛋白MTRAP和AMA 1的分泌，并且在与红细胞接触时，观察到MTRAP的分泌，而不是AMA 1。APH缺失的裂殖子能够附着于红细胞并使其变形，这与观察到的MTRAP分泌一致。形成紧密连接，但裂殖子内化到红细胞后的棘红细胞增多症显著减少，与观察到的AMA 1分泌的缺乏一致。结合我们观察到APH主要与MTRAP共定位，但与AMA 1较少共定位，我们提出APH直接参与MTRAP分泌;而APH在AMA 1分泌中的任何作用在疟原虫中都是间接的。
Plasmodium, the causative agents of malaria, are obligate intracellular organisms. In humans, pathogenesis is caused by the blood stage parasite, which multiplies within erythrocytes, thus erythrocyte invasion is an essential developmental step. Merozoite form parasites released into the blood stream coordinately secrets a panel of proteins from the microneme secretory organelles for gliding motility, establishment of a tight junction with a target naive erythrocyte, and subsequent internalization. A protein identified inToxoplasma gondiifacilitates microneme fusion with the plasma membrane for exocytosis; namely, acylated pleckstrin homology domain-containing protein (APH). To obtain insight into the differential microneme discharge by malaria parasites, in this study we analyzed the consequences of APH deletion in the rodent malaria model,Plasmodium yoelii, using a DiCre-based inducible knockout method. We found that APH deletion resulted in a reduction in parasite asexual growth and erythrocyte invasion, with some parasites retaining the ability to invade and grow without APH. APH deletion impaired the secretion of microneme proteins, MTRAP and AMA1, and upon contact with erythrocytes the secretion of MTRAP, but not AMA1, was observed. APH-deleted merozoites were able to attach to and deform erythrocytes, consistent with the observed MTRAP secretion. Tight junctions were formed, but echinocytosis after merozoite internalization into erythrocytes was significantly reduced, consistent with the observed absence of AMA1 secretion. Together with our observation that APH largely colocalized with MTRAP, but less with AMA1, we propose that APH is directly involved in MTRAP secretion; whereas any role of APH in AMA1 secretion is indirect inPlasmodium.