The protozoan parasite Plasmodium, the causative agent of malaria, undergoes an obligatory stage of intra-hepatic development before initiating a blood-stage infection. Productive invasion of hepatocytes involves the formation of a parasitophorous vacuole (PV) generated by the invagination of the host cell plasma membrane. Surrounded by the PV membrane (PVM), the parasite undergoes extensive replication. During intracellular development in the hepatocyte, the parasites provoke the Plasmodium-associated autophagy-related (PAAR) response. This is characterized by a long-lasting association of the autophagy marker protein, and ATG8 family member, LC3B with the PVM. LC3B localization at the PVM does not follow the canonical autophagy pathway since upstream events specific to canonical autophagy are dispensable. Here, we describe that LC3B localization at the PVM of Plasmodium parasites requires the V-ATPase and its interaction with ATG16L1. The WD40 domain of ATG16L1 is crucial for its recruitment to the PVM. Thus, we provide new mechanistic insight into the previously described PAAR response targeting Plasmodium liver stage parasites.

中文翻译：

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伯氏疟原虫肝期寄生虫寄生液泡膜的 LC3B 标记取决于 V-ATP 酶和 ATG16L1


原生动物寄生虫疟原虫是疟疾的病原体，在开始血液阶段感染之前要经历肝内发育的必然阶段。肝细胞的生产性侵袭涉及宿主细胞质膜内陷产生的寄生液泡（PV）的形成。寄生虫被 PV 膜 (PVM) 包围，进行广泛的复制。在肝细胞的细胞内发育过程中，寄生虫会引发疟原虫相关的自噬相关（PAAR）反应。其特征在于自噬标记蛋白和 ATG8 家族成员 LC3B 与 PVM 的长期关联。 PVM 上的 LC3B 定位不遵循规范自噬途径，因为特定于规范自噬的上游事件是可有可无的。在这里，我们描述了 LC3B 在疟原虫寄生虫 PVM 上的定位需要 V-ATP 酶及其与 ATG16L1 的相互作用。 ATG16L1 的 WD40 结构域对于其招募到 PVM 至关重要。因此，我们为先前描述的针对疟原虫肝期寄生虫的 PAAR 反应提供了新的机制见解。