Abstract
Parasites of the phylum Apicomplexa cause important diseases including malaria, cryptosporidiosis and toxoplasmosis. These intracellular pathogens inject the contents of an essential organelle, the rhoptry, into host cells to facilitate invasion and infection. However, the structure and mechanism of this eukaryotic secretion system remain elusive. Here, using cryo-electron tomography and subtomogram averaging, we report the conserved architecture of the rhoptry secretion system in the invasive stages of two evolutionarily distant apicomplexans, Cryptosporidium parvum and Toxoplasma gondii. In both species, we identify helical filaments, which appear to shape and compartmentalize the rhoptries, and an apical vesicle (AV), which facilitates docking of the rhoptry tip at the parasite’s apical region with the help of an elaborate ultrastructure named the rhoptry secretory apparatus (RSA); the RSA anchors the AV at the parasite plasma membrane. Depletion of T. gondii Nd9, a protein required for rhoptry secretion, disrupts the RSA ultrastructure and AV-anchoring. Moreover, T. gondii contains a line of AV-like vesicles, which interact with a pair of microtubules and accumulate towards the AV, leading to a working model for AV-reloading and discharging of multiple rhoptries. Together, our analyses provide an ultrastructural framework to understand how these important parasites deliver effectors into host cells.
Highlights
Parasites of the phylum Apicomplexa cause important diseases including malaria, cryptosporidiosis and toxoplasmosis
Several important questions remain unanswered—(i) How is the defined shape of rhoptry neck maintained? (ii) Are the apparent roles of the apical vesicle (AV) and the apical rosette in mediating rhoptry tip docking conserved among apicomplexans, or even in T. gondii tachyzoites? (iii) If the apical rosette does mediate the secretion of rhoptry contents across the membranes of the AV and the parasite plasma membrane, how does its structural organization support this function? and (iv) How are multiple discharge events achieve in apicomplexans like T. gondii, which possess several rhoptries?
We report the consistent presence of an AV and an apical rosette in both organisms; the latter is a part of a larger proteinaceous feature, which we named the rhoptry secretory apparatus (RSA)
Summary
Parasites of the phylum Apicomplexa cause important diseases including malaria, cryptosporidiosis and toxoplasmosis. Micronemes of C. parvum showed distinct filaments lining the luminal side of their bounding membranes, a feature not observed in T. gondii (Supplementary Fig. 3).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
