An Alveolata secretory machinery adapted to parasite host cell invasion

Article Article scientifique Article An Alveolata secretory machinery adapted to parasite host cell invasion eng 2021-01-25 2021-04 author Aquilini Eleonora author Cova Marta Mendonça author Mageswaran Shrawan Kumar 0000-0002-0803-7129 author Dos Santos Pacheco Nicolas 0000-0003-1959-194X author Sparvoli Daniela 0000-0002-5992-3753 author Penarete-Vargas Diana Marcela author Najm Rania 0000-0002-7685-0760 author Graindorge Arnault 0000-0002-6076-3646 author Suarez Catherine 0000-0003-2984-7881 author Maynadier Marjorie 0000-0002-1825-3095 author Berry-Sterkers Laurence author Urbach Serge 0000-0001-8663-2006 author Ruga Fahy Pilar 133641 Services communs de la faculté de médecine (SCMU) author Guérin Amandine 0000-0001-8307-5099 410740 Département de microbiologie et médecine moléculaire (MIMOL) author Striepen Boris author Dubremetz Jean-François author Chang Yi-Wei 0000-0003-2391-473X author Turkewitz Aaron P. author Lebrun Maryse 0000-0002-0962-0156 425-434 10.1038/s41564-020-00854-z 33495622 2058-5276 PMC8886610 https://www.nature.com/articles/s41564-020-00854-z Apicomplexa are unicellular eukaryotes and obligate intracellular parasites, including Plasmodium (the causative agent of malaria) and Toxoplasma (one of the most widespread zoonotic pathogens). Rhoptries, one of their specialized secretory organelles, undergo regulated exocytosis during invasion<a href="https://www.nature.com/articles/s41564-020-00854-z#ref-CR1" rel="noopener noreferrer" target="_blank">1</a>. Rhoptry proteins are injected directly into the host cell to support invasion and subversion of host immune function<a href="https://www.nature.com/articles/s41564-020-00854-z#ref-CR2" rel="noopener noreferrer" target="_blank">2</a>. The mechanism by which they are discharged is unclear and appears distinct from those in bacteria, yeast, animals and plants. Here, we show that rhoptry secretion in Apicomplexa shares structural and genetic elements with the exocytic machinery of ciliates, their free-living relatives. Rhoptry exocytosis depends on intramembranous particles in the shape of a rosette embedded into the plasma membrane of the parasite apex. Formation of this rosette requires multiple non-discharge (Nd) proteins conserved and restricted to Ciliata, Dinoflagellata and Apicomplexa that together constitute the superphylum Alveolata. We identified Nd6 at the site of exocytosis in association with an apical vesicle. Sandwiched between the rosette and the tip of the rhoptry, this vesicle appears as a central element of the rhoptry secretion machine. Our results describe a conserved secretion system that was adapted to provide defence for free-living unicellular eukaryotes and host cell injection in intracellular parasites. Alveolata / classification Alveolata / physiology Alveolata / ultrastructure Cell Membrane / metabolism Exocytosis Host-Parasite Interactions Humans Organelles / metabolism Protozoan Proteins / genetics Protozoan Proteins / metabolism Secretory Vesicles / metabolism Dewey 610 NIGMS NIH HHS R01 GM105783 NIAID NIH HHS R01 AI112427 European Commission Unravelling the secretion machinery for virulence factors in apicomplexan parasites 833309 KissAndSpitRhoptry EU H2020 3 Faculté de médecine 2 false 1411 Pouvoir pathogène du parasite cryptosporidium 1046 https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD022713 https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD022725 Nature microbiology 6 4 13f3c623-c04a-43ea-9cbc-a5d4a03449fd Article (Published version) Restricted Article-scientifique-from-crossref.pdf 20171190 application/pdf c716dd9b25eed8969b28f680760d5bd30e6fe7da5185e3c51e5c9391c18ad958 aeb84429-3a74-43f5-9653-a3df1a951fbf Article (Accepted version) Public nihms-1672971.pdf 6132800 application/pdf f2b7748c9ccd8c2bc8d0bdedd4b345c81ba1a74750b25d18b66cc3a1c6a9569c 5f629db3-4b65-4a56-a9cc-ae3c9e92b1e3 Supplemental data Public NIHMS1672971-supplement-Supp_Table_.docx 15982 application/vnd.openxmlformats-officedocument.wordprocessingml.document Supplementary Table 1. Putative gene orthologues found in Toxoplasma gondii and Plasmodium falciparum using Paramecium protein sequences. b49267d072a9d17f7590ceae3c85704de257ef0885da80484ff4cd837b72754d 99083030-b175-4b8b-bc3e-7412fe5fbe42 Supplemental data Public NIHMS1672971-supplement-Supp_Table_.xlsx 3070432 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet Supplementary Table 2 Mass spectrometry data of Nd9 immunoprecipitation. 48b5d20d6fb736f01dc47f83da0435fe1d5b166f7ffd0a4e0d4480d1dca57b19 b40e313e-7056-4a83-8283-915df357ff6f Supplemental data Public NIHMS1672971-supplement-Supp_Table_1.xlsx 3358852 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet Supplementary Table 3 Mass spectrometry data of NdP1 immunoprecipitation. b9791b9afc79109977dbadc83f5328048ff0d05505f1e0788ac6df9d0ad05330 34d5f00c-98c5-4ecc-bf2e-bb753a3bfafc Supplemental data Public NIHMS1672971-supplement-Supp_Table_2.xlsx 15911 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet Supplementary Table 4 List of primers used. 86ec07d1cb9934e3391b9c743abdbe76b2926d5ed2d529a81dcdf82b57b6885b 4f584d2d-d730-4aff-8351-bffed9304f8e Appendix Public NIHMS1672971-supplement-Extended_fi.docx 1810193 application/vnd.openxmlformats-officedocument.wordprocessingml.document Extended figs captions supp methods text and refs. f40194d0fb6827433b70d64c7f1436b2ff2283ccda1d257eb8bde0418793880c 44ca1fc1-d3e5-43b5-a978-625d559a0c63 Appendix Public 41564_2020_854_MOESM1_ESM.pdf 855527 application/pdf Supplementary information: Supplementary Fig. 1, Table 1, Text, Methods and references. 6e29852a90ba17f7a20a5b7ad9c0050538aec0b3c03a443c9c02b0fddba0a32a 05302828-2e5f-4576-ac9b-65074d08a381 Appendix Public NIHMS1672971-supplement-Supp_fig_1.docx 302461 application/vnd.openxmlformats-officedocument.wordprocessingml.document Supplementary Fig 1 78319e34f138209e545dca764d8a67ebdc65e3605ff8f24a20a282ee63c72ee1 1df5077e-17c6-4cc2-a434-f2e7136167ce Supplemental data Public 41564_2020_854_MOESM7_ESM.xlsx 12348 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet Source Data Fig. 1: Statistical source data. 2db4c88c3b1d4e30984073993ff918917c9cee594c6dacae65ff96762dae3de4 2550ad40-cec6-42ea-b4c7-ff5a0551d9e0 Supplemental data Public 41564_2020_854_MOESM8_ESM.pdf 196682 application/pdf Source Data Fig. 1 Unprocessed western blots. 15a54d93c0545e33228e239c0320162288e31c8fdc699bc9d2945fb2b3a70990 f1214594-5202-4566-9516-ea248568fad0 Supplemental data Public 41564_2020_854_MOESM9_ESM.xlsx 13354 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet Source Data Fig. 2 Statistical source data. b84c0f4cf0aebfea78685a3da72a5c687c30b5f27b7bc2db52606e63dc704d9f add3b1ea-801c-4fef-90ee-d3beb373b985 Supplemental data Public 41564_2020_854_MOESM10_ESM.xlsx 12182 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet Source Data Fig. 3 Statistical source data. cf9a5a7bc5e2e3e4b99b2afe642ac5374371915576fcc3edbd9872295b44f644 51a2b01e-1e2d-424e-9f4c-633ca5ba241e Supplemental data Public 41564_2020_854_MOESM11_ESM.pdf 1022739 application/pdf Source Data Extended Data Fig. 1 Amino acid sequence alignments. dcc65434caf6054cc06281638f6d96a4c9b569336fb9538193aa3079ebe4e102 9f54bdb7-62c2-4c85-a454-8f49a781f5b6 Supplemental data Public 41564_2020_854_MOESM12_ESM.pdf 513931 application/pdf Source Data Extended Data Fig. 2 Unprocessed gels and western blots. 3a65f8baf8869818a5543c6ad600e748a2f560b70a7b3e82f3e8a32eae808f17 d375a259-0864-4b68-a16a-6e627380d94d Supplemental data Public 41564_2020_854_MOESM13_ESM.xlsx 27214 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet Source Data Extended Data Fig. 3 Statistical source data. 3712e6fc5c2c5604588ad7a16ef06fd56ac04f346d67c5d12a60c91997216605 0d415b6d-bd54-4733-a491-6cc6ca472cb4 Supplemental data Public 41564_2020_854_MOESM14_ESM.pdf 449776 application/pdf Source Data Extended Data Fig. 5 Unprocessed gels and western blot. 90c44f5a53a8d26a5d5a92fb0ac7be6683b4f0b0d05944d0fe66aac29e94c987 059734bc-4ebd-4929-bef4-b6ae7582bb40 Supplemental data Public 41564_2020_854_MOESM15_ESM.pdf 473074 application/pdf Source Data Extended Data Fig. 6 Unprocessed gels and western blots. e6ebfe3ba12d8b7edff360e9cefb2d7ee56f02f2fe980e083f9ac03c4e240daa f90f2ce4-e6ae-471a-89fa-d7eee9578a2e Supplemental data Public 41564_2020_854_MOESM16_ESM.xlsx 23143 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet Source Data Extended Data Fig. 7 Statistical source data. a34c9baa876465aed5ebc2b76ecacb2f72925fefa99b2da23f9e8f2a474f9e00 507eb9b8-b382-4e36-ba56-14955481a7ed Supplemental data Public 41564_2020_854_MOESM17_ESM.pdf 424406 application/pdf Source Data Extended Data Fig. 7 Unprocessed western blots. fcaecd3e0cba6d43157fb1470b35b44a88a653a8b0eb2db8c5cedd63197ef381 649068a5-6654-4020-b94d-f2b4931a54b6 Supplemental data Public 41564_2020_854_MOESM18_ESM.pdf 650646 application/pdf Source Data Extended Data Fig. 8 Unprocessed gels and western blots. 3dd3d2d453b7f5f73c5a8011db5cb8ec3b2af51928208a4257f6b273ca37435c openAccess Faculté de médecine

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An Alveolata secretory machinery adapted to parasite host cell invasion	Nature microbiology			2021	177	396

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