Endocytosed lipids induce cell aggregation via filopodia retraction in a close relative of animals

Capsaspora owczarzaki is a protist that may both reveal aspects of animal evolution and curtail the spread of schistosomiasis. Capsaspora exhibits a regulated aggregative behavior reminiscent of cellular aggregation in some animals-a process that might have contributed to the origin of animals. This aggregative behavior may also be vital for Capsaspora to colonize the intermediate host of parasitic schistosomes and potentially prevent the spread of schistosomiasis. Both applications demand elucidation of the mechanisms underlying Capsaspora aggregation. Toward this goal, we evaluated the chemical properties of lipid cues that activate aggregation. We found that a range of zwitterionic lipids induced this behavior, revealing that aggregation is activated by diverse lipid-rich conditions. Furthermore, we demonstrated that aggregation in Capsaspora requires clathrin-mediated endocytosis, highlighting the potential significance of endocytosis-linked cellular signaling in recent animal ancestors. Finally, we found that aggregation is initiated independently of protein translation, suggesting post-translational activation of filopodial retraction. Together, our findings illuminate the molecular and cellular basis of Capsaspora's aggregative behavior, with implications for the evolution of animal multicellularity and the transmission of parasites.