An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites
An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites
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DOI：
10.7554/elife.23485
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发表时间：
2017-02-21
期刊：
影响因子：
7.7
通讯作者：
Desai, Sanjay A.
中科院分区：
文献类型：
--
作者：
Ito, Daisuke;Schureck, Marc A.;Desai, Sanjay A.
疟原虫通过在红细胞内生长和复制逃避免疫检测。红细胞侵入后，胞内病原体必须增加宿主细胞从血浆中摄取营养物质。在这里，我们报告说，寄生虫编码的RhopH复合物有助于入侵和通道介导的营养吸收。由于rhoph 2和rhoph 3基因敲除在人类恶性疟原虫病原体中不可行，我们使用条件性敲除来确定编码的蛋白质是必需的，并鉴定其阶段特异性功能。我们排除了RhopH 2和CLAG 3在红细胞侵袭中的假定作用，但暗示RhopH 3通过配体-受体相互作用或随后的寄生虫内化做出贡献。这些蛋白质然后通过输出易位子运输到宿主膜，在那里它们形成营养通道。RhopH 2或RhopH 3的敲除破坏整个复合物，干扰细胞器靶向和随后的运输。针对这种复合物的治疗应该在病原体周期的两个关键点攻击病原体。
Malaria parasites evade immune detection by growth and replication within erythrocytes. After erythrocyte invasion, the intracellular pathogen must increase host cell uptake of nutrients from plasma. Here, we report that the parasite-encoded RhopH complex contributes to both invasion and channel-mediated nutrient uptake. As rhoph2 and rhoph3 gene knockouts were not viable in the human P. falciparum pathogen, we used conditional knockdowns to determine that the encoded proteins are essential and to identify their stage-specific functions. We exclude presumed roles for RhopH2 and CLAG3 in erythrocyte invasion but implicate a RhopH3 contribution either through ligand-receptor interactions or subsequent parasite internalization. These proteins then traffic via an export translocon to the host membrane, where they form a nutrient channel. Knockdown of either RhopH2 or RhopH3 disrupts the entire complex, interfering with organellar targeting and subsequent trafficking. Therapies targeting this complex should attack the pathogen at two critical points in its cycle.