Lehrstuhl für experimentelle Parasitologie, Ludwig-Maximilians-Universität, LMU, Tierärztliche Fakultät, München, Germany.
Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity & Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom.
PLoS Biol. 2019 Jun 24;17(6):e3000060. doi: 10.1371/journal.pbio.3000060. eCollection 2019 Jun.
Apicomplexan parasites invade host cells in an active process involving their ability to move by gliding motility. While the acto-myosin system of the parasite plays a crucial role in the formation and release of attachment sites during this process, there are still open questions regarding the involvement of other mechanisms in parasite motility. In many eukaryotes, a secretory-endocytic cycle leads to the recycling of receptors (integrins), necessary to form attachment sites, regulation of surface area during motility, and generation of retrograde membrane flow. Here, we demonstrate that endocytosis operates during gliding motility in Toxoplasma gondii and appears to be crucial for the establishment of retrograde membrane flow, because inhibition of endocytosis blocks retrograde flow and motility. We demonstrate that extracellular parasites can efficiently incorporate exogenous material, such as labelled phospholipids, nanogold particles (NGPs), antibodies, and Concanavalin A (ConA). Using labelled phospholipids, we observed that the endocytic and secretory pathways of the parasite converge, and endocytosed lipids are subsequently secreted, demonstrating the operation of an endocytic-secretory cycle. Together our data consolidate previous findings, and we propose an additional model, working in parallel to the acto-myosin motor, that reconciles parasite motility with observations in other eukaryotes: an apicomplexan fountain-flow-model for parasite motility.
顶复门寄生虫通过滑行运动主动侵入宿主细胞，在此过程中，它们的运动能力依赖于虫体的肌动球蛋白系统。虽然寄生虫的肌动球蛋白系统在附着部位的形成和释放过程中起着至关重要的作用，但关于其他机制在寄生虫运动中的参与，仍存在一些悬而未决的问题。在许多真核生物中，一个分泌-内吞循环导致受体（整合素）的循环利用，这对于形成附着部位、在运动过程中调节表面积以及产生逆行膜流是必需的。在这里，我们证明了内吞作用在刚地弓形虫的滑行运动中起作用，并且似乎对逆行膜流的建立至关重要，因为内吞作用的抑制会阻断逆行流和运动。我们证明了体外寄生虫可以有效地摄取外源性物质，如标记的磷脂、纳米金颗粒（NGP）、抗体和伴刀豆球蛋白 A（ConA）。使用标记的磷脂，我们观察到寄生虫的内吞作用和分泌途径汇聚，并且内吞的脂质随后被分泌，证明了内吞-分泌循环的运作。总之，我们的数据巩固了以前的发现，并提出了一个额外的模型，与肌动球蛋白马达平行工作，该模型将寄生虫的运动与其他真核生物的观察结果协调起来：顶复门寄生虫的喷泉流动模型。
