Digestive vacuole biogenesis in the malaria parasite

描述（由申请人提供）：本申请旨在了解疟疾寄生虫恶性疟原虫消化泡（DV）的生物发生。这种酸性的溶酶体样细胞器负责降解从宿主红细胞摄取的大量血红蛋白。DV也是最大的和历史上最有临床应用价值的抗疟药家族4-氨基喹啉的作用部位。尽管这种细胞器的重要性，寄生虫的发展和抗疟化疗，目前知之甚少的生物合成的寄生虫蛋白质和宿主细胞胞质溶胶的成分是如何在红细胞内的生命周期期间交付到DV。我建议确定哪些贩运步骤是必不可少的运输寄生虫和宿主细胞蛋白质的DV的遗传和化学破坏的定义阶段的细胞内运输。这些研究将使我们能够解决的假设，寄生虫蛋白质运输到DV的一个途径依赖于蛋白质分泌和分选的Sec和Vps组件。我们的第二个主要假设是血红蛋白和一些宿主红细胞胞质溶胶组分的摄取通过动力蛋白依赖性内吞作用进行。

DESCRIPTION (provided by applicant): This application aims to understand the biogenesis of the digestive vacuole (DV) of the malaria parasite, Plasmodium falciparum. This acidic, lysosomal-like organelle is responsible for the degradation of large quantities of hemoglobin ingested from the host erythrocyte. The DV is also the site of action of the largest and historically the most clinically useful family of antimalarial drugs, the 4-aminoquinolines. Despite the importance of this organelle to parasite development and antimalarial chemotherapy, little is currently known about how both biosynthetic parasite proteins and components of the host cell cytosol are delivered to the DV during the intraerythrocytic lifecycle. I propose to determine which trafficking steps are essential for the transport of parasite and host cell proteins to the DV by genetic and chemical disruption of defined stages of intracellular transport. These studies will enable us to address the hypothesis that one pathway of parasite protein trafficking to the DV relies upon the Sec and Vps components of protein secretion and sorting. Our second major hypothesis is that uptake of hemoglobin and some host erythrocyte cytosol components proceeds via dynamin-dependent endocytosis.