Prior to initiating symptomatic malaria, a single Plasmodium sporozoite infects a hepatocyte and develops into thousands of merozoites, in part by scavenging host resources, likely delivered by vesicles. Here, we demonstrate that host microtubules (MTs) dynamically reorganize around the developing liver stage (LS) parasite to facilitate vesicular transport to the parasite. Using a genome-wide CRISPR-Cas9 screen, we identified host regulators of cytoskeleton organization, vesicle trafficking, and ER/Golgi stress that regulate LS development. Foci of γ-tubulin localized to the parasite periphery; depletion of centromere protein J (CENPJ), a novel regulator identified in the screen, exacerbated this re-localization and increased infection. We demonstrate that the Golgi acts as a non-centrosomal MT organizing center (ncMTOC) by positioning γ-tubulin and stimulating MT nucleation at parasite periphery. Together, these data support a model where the Plasmodium LS recruits host Golgi to form MT-mediated conduits along which host organelles are recruited to PVM and support parasite development.

在引发症状性疟疾之前，单个疟原虫子孢子会感染肝细胞并发育成数千个裂殖子，部分是通过清除宿主资源（可能是由囊泡传递）来实现的。在这里，我们证明宿主微管（MT）围绕发育中的肝脏阶段（LS）寄生虫动态重组，以促进囊泡转运至寄生虫。使用全基因组 CRISPR-Cas9 筛选，我们确定了调节 LS 发育的细胞骨架组织、囊泡运输和 ER/高尔基体应激的宿主调节因子。γ-微管蛋白的病灶位于寄生虫周围；着丝粒蛋白 J (CENPJ) 是筛选中发现的一种新型调节因子，其耗竭加剧了这种重新定位并增加了感染。我们证明高尔基体通过定位 γ-微管蛋白并刺激寄生虫周围的 MT 成核而充当非中心体 MT 组织中心 (ncMTOC)。总之，这些数据支持了一个模型，其中疟原虫LS 招募宿主高尔基体形成 MT 介导的管道，沿着该管道宿主细胞器被招募到 PVM 并支持寄生虫的发育。