Stable endocytic structures navigate the complex pellicle of apicomplexan parasites.

Apicomplexan parasites have immense impacts on humanity, but their basic cellular processes are often poorly understood. Where endocytosis occurs in these cells, how conserved this process is with other eukaryotes, and what the functions of endocytosis are across this phylum are major unanswered questions. Using the apicomplexan model Toxoplasma, we identified the molecular composition and behavior of unusual, fixed endocytic structures. Here, stable complexes of endocytic proteins differ markedly from the dynamic assembly/disassembly of these machineries in other eukaryotes. We identify that these endocytic structures correspond to the 'micropore' that has been observed throughout the Apicomplexa. Moreover, conserved molecular adaptation of this structure is seen in apicomplexans including the kelch-domain protein K13 that is central to malarial drug-resistance. We determine that a dominant function of endocytosis in Toxoplasma is plasma membrane homeostasis, rather than parasite nutrition, and that these specialized endocytic structures originated early in infrakingdom Alveolata likely in response to the complex cell pellicle that defines this medically and ecologically important ancient eukaryotic lineage

Stable endocytic structures navigate the complex pellicle of apicomplexan parasites

Acknowledgements: This work was supported by the Wellcome Trust, United Kingdom, Investigator award 214298/Z/18/Z to R.F.W., a Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) grant 464878930 to S.G., and a DFG Equipment grant INST 86/1831-1 to Prof. Markus Meissner. B.N.M.S. was supported by a Gates Cambridge Scholarship, and K.B. was supported by the Leverhulme Early Career Fellowship (ECF-2015-562) provided jointly by the Isaac Newton Trust and the Leverhulme Trust. M.S.R. and J.H. was supported by Wellcome Trust grants 086598 and 214272 to M.S.R. and a Wellcome Trust Strategic Award 100140 to the Cambridge Institute for Medical Research (CIMR). N.R.Z. was supported by Wellcome Trust grant WT 207455/Z/17/Z. C.M.K. was supported by a Canada Vanier Graduate Scholarship and J.B.D. is supported by the Canada Research Chair (Tier II) in Evolutionary Cell Biology and by the Natural Sciences and Engineering Research Council of Canada (RES0043758, RES0046091). Y.R-C. was supported by NIH awards F31AI152297 and T32AI007528. We thank VEuPathDB for their invaluable Informatics Resources, and Markus Meissner, Christine Hopp, Nicola Hodson, Julian Rayner, Mirko Singer and David Warhurst for useful discussions, and Cornelia Niemann and Karin Müller for assistance with electron microscopy.AbstractApicomplexan parasites have immense impacts on humanity, but their basic cellular processes are often poorly understood. Where endocytosis occurs in these cells, how conserved this process is with other eukaryotes, and what the functions of endocytosis are across this phylum are major unanswered questions. Using the apicomplexan model Toxoplasma, we identified the molecular composition and behavior of unusual, fixed endocytic structures. Here, stable complexes of endocytic proteins differ markedly from the dynamic assembly/disassembly of these machineries in other eukaryotes. We identify that these endocytic structures correspond to the ‘micropore’ that has been observed throughout the Apicomplexa. Moreover, conserved molecular adaptation of this structure is seen in apicomplexans including the kelch-domain protein K13 that is central to malarial drug-resistance. We determine that a dominant function of endocytosis in Toxoplasma is plasma membrane homeostasis, rather than parasite nutrition, and that these specialized endocytic structures originated early in infrakingdom Alveolata likely in response to the complex cell pellicle that defines this medically and ecologically important ancient eukaryotic lineage.</jats:p