Apicomplexan motility depends on the operation of an endocytic-secretory cycle

ABSTRACT Apicomplexan parasites invade host cells in an active process, involving their ability to move by gliding motility and invasion. 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, such as how the force powering motility is generated. In many eukaryotes a secretory-endocytic cycle leads to 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, since inhibition of endocytosis blocks retrograde flow and motility. We identified lysophosphatidic acid (LPA) as a potent stimulator of endocytosis and demonstrate that extracellular parasites can efficiently incorporate exogenous material, such as nanogold particles. Furthermore, we show that surface proteins of the parasite are recycled during this process. Interestingly, the endocytic and secretory pathways of the parasite converge, and endocytosed material is subsequently secreted, demonstrating the operation of an endocytic-secretory cycle. Together our data consolidate previous findings and we propose a novel model that reconciles parasite motility with observations in other eukaryotes: the fountain-flow-model for apicomplexan parasite motility.