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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,\n                    <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                    and\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    . 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\u2019s 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\n                    <jats:italic>T. gondii<\/jats:italic>\n                    Nd9, a protein required for rhoptry secretion, disrupts the RSA ultrastructure and AV-anchoring. Moreover,\n                    <jats:italic>T. gondii<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-25309-9","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T06:05:02Z","timestamp":1629180302000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["In situ ultrastructures of two evolutionarily distant apicomplexan rhoptry secretion systems"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0803-7129","authenticated-orcid":false,"given":"Shrawan Kumar","family":"Mageswaran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandine","family":"Gu\u00e9rin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam M.","family":"Theveny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0594-4065","authenticated-orcid":false,"given":"William David","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryse","family":"Lebrun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Striepen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2391-473X","authenticated-orcid":false,"given":"Yi-Wei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"25309_CR1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S1473-3099(14)70772-8","volume":"15","author":"W Checkley","year":"2015","unstructured":"Checkley, W. et al. A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium. Lancet Infect. Dis. 15, 85\u201394 (2015).","journal-title":"Lancet Infect. Dis."},{"key":"25309_CR2","doi-asserted-by":"publisher","first-page":"e1001920","DOI":"10.1371\/journal.pmed.1001920","volume":"12","author":"PR Torgerson","year":"2015","unstructured":"Torgerson, P. R. et al. World Health Organization Estimates of the Global and Regional Disease Burden of 11 Foodborne Parasitic Diseases, 2010: a data synthesis. PLoS Med. 12, e1001920 (2015).","journal-title":"PLoS Med."},{"key":"25309_CR3","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/S0140-6736(19)31097-9","volume":"394","author":"DJ Weiss","year":"2019","unstructured":"Weiss, D. J. et al. Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum, 2000\u201317: a spatial and temporal modelling study. 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