The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Victoria, Australia.
Department of Medical Biology, The University of Melbourne, Parkville, 3052, Victoria, Australia.
Commun Biol. 2022 Apr 7;5(1):333. doi: 10.1038/s42003-022-03290-3.
RhopH complexes consists of Clag3, RhopH2 and RhopH3 and are essential for growth of Plasmodium falciparum inside infected erythrocytes. Proteins are released from rhoptry organelles during merozoite invasion and trafficked to the surface of infected erythrocytes and enable uptake of nutrients. RhopH3, unlike other RhopH proteins, is required for parasite invasion, suggesting some cellular processes RhopH proteins function as single players rather than a complex. We show the RhopH complex has not formed during merozoite invasion. Clag3 is directly released into the host cell cytoplasm, whilst RhopH2 and RhopH3 are released into the nascent parasitophorous vacuole. Export of RhopH2 and RhopH3 from the parasitophorous vacuole into the infected erythrocyte cytoplasm enables assembly of Clag3/RhopH2/RhopH3 complexes and incorporation into the host cell membrane concomitant with activation of nutrient uptake. This suggests compartmentalisation prevents premature channel assembly before intact complex is assembled at the host cell membrane.
RhopH 复合物由 Clag3、RhopH2 和 RhopH3 组成，对于疟原虫在感染的红细胞内生长是必不可少的。蛋白质在裂殖子入侵期间从棒状体细胞器中释放出来，并被运送到感染的红细胞表面，从而使营养物质得以摄取。与其他 RhopH 蛋白不同，RhopH3 是寄生虫入侵所必需的，这表明 RhopH 蛋白的一些细胞过程作为单个参与者发挥作用，而不是作为一个复合物。我们表明，在裂殖子入侵过程中，RhopH 复合物尚未形成。Clag3 直接释放到宿主细胞质中，而 RhopH2 和 RhopH3 则释放到新形成的胞质中。RhopH2 和 RhopH3 从胞质中输出到感染的红细胞细胞质中，使 Clag3/RhopH2/RhopH3 复合物组装并与宿主细胞膜结合，同时激活营养物质摄取。这表明区室化可以防止在完整复合物在宿主细胞膜上组装之前过早地进行通道组装。
