Sustained rhoptry docking and discharge requires Toxoplasma gondii intraconoidal microtubule-associated proteins

Article Article scientifique Article Sustained rhoptry docking and discharge requires Toxoplasma gondii intraconoidal microtubule-associated proteins eng 2024-01-09 2024-01-09 author Dos Santos Pacheco Nicolas 0000-0003-1959-194X 880386 author Tell I Puig Albert 0009-0001-3564-9542 974597 Département de microbiologie et médecine moléculaire (MIMOL) author Guérin Amandine 0000-0001-8307-5099 410740 Département de microbiologie et médecine moléculaire (MIMOL) author Martinez Matthew 0000-0003-2559-1794 author Maco Bohumil 0000-0001-8444-313X 863802 Services communs de la faculté de médecine (SCMU) author Tosetti Nicolo 828676 author Delgado Betancourt Estefania 0000-0002-1273-3733 403258 Département de microbiologie et médecine moléculaire (MIMOL) author Lunghi Matteo 0000-0002-9338-9929 868427 author Striepen Boris 0000-0002-7426-432X author Chang Yi-Wei 0000-0003-2391-473X author Soldati-Favre Dominique 0000-0003-4156-2109 135114 Département de microbiologie et médecine moléculaire (MIMOL) 379 10.1038/s41467-023-44631-y 38191574 2041-1723 https://www.nature.com/articles/s41467-023-44631-y In Apicomplexa, rhoptry discharge is essential for invasion and involves an apical vesicle (AV) docking one or two rhoptries to a macromolecular secretory apparatus. Toxoplasma gondii is armed with 10–12 rhoptries and 5-6 microtubule-associated vesicles (MVs) presumably for iterative rhoptry discharge. Here, we have addressed the localization and functional significance of two intraconoidal microtubule (ICMT)-associated proteins instrumental for invasion. Mechanistically, depletion of ICMAP2 leads to a dissociation of the ICMTs, their detachment from the conoid and dispersion of MVs and rhoptries. ICMAP3 exists in two isoforms that contribute to the control of the ICMTs length and the docking of the two rhoptries at the AV, respectively. This study illuminates the central role ICMTs play in scaffolding the discharge of multiple rhoptries. This process is instrumental for virulence in the mouse model of infection and in addition promotes sterile protection against T. gondii via the release of key effectors inducing immunity. Dewey 616 Swiss National Science Foundation An integrated approach to elucidate the molecular mechanisms governing host cell invasion and egress by the Apicomplexa 185325 CH Projects European Commission Molecular Basis of Toxoplasma gondii Encystation and Persistence 695596 ToxoPersist EU H2020 54 Département de microbiologie et médecine moléculaire 21B false 443 Biologie d'un parasite intracellulaire obligatoire 773 Nature communications 15 1 ddc49a62-b4df-430a-844b-7ee93f15d3e5 Article (Published version) Public Article-scientifique-from-crossref.pdf 7819123 application/pdf CC BY-4.0 a16626265184caf6f70db4e4c20586936713665c91005484b37490ada6e3023b 9bd2a583-21e9-45d1-8364-3addec0e55bf Supplemental data Public 41467_2023_44631_MOESM1_ESM.pdf 9207472 application/pdf ae044531b3ece1a9f338bfbe8fd08cb39952975bfd9a7213a8259121866142b3 15a6a76b-42db-4fe5-b97d-5f8326d2dbc7 Supplemental data Public 41467_2023_44631_MOESM4_ESM.mov 25636253 video/quicktime f894e1433c355137f10ca3d6c4ee53ebde8217dec3edf13e363040e32a7a6ad5 770ef6c3-c249-47b2-b7c5-b9d67574e8dd Supplemental data Public 41467_2023_44631_MOESM5_ESM.mov 27025622 video/quicktime 591fd114ae36e206f1cc31083814b15e3b5085685038dd25f9f6aa392fc181b4 0f2efbda-88ff-4d4e-97a6-c147f6704b88 Supplemental data Public 41467_2023_44631_MOESM6_ESM.mp4 15339684 video/mp4 dbcfc2486f02f96ff4f84a5c3ba524ed1c59fb7d605decf4c42d549ff561550b 0aa2390d-fcfc-47a9-b67f-cddc4884e035 Supplemental data Public 41467_2023_44631_MOESM7_ESM.mp4 18451685 video/mp4 c7e2f3b68bf9e5357c6f57f6415cd397d482f3c719b75285d8e63a386ec48c4e 1a0cb914-36d0-411a-aaaa-e84f3cfb5144 Supplemental data Public 41467_2023_44631_MOESM8_ESM.mov 93522660 video/quicktime abc3e0929c9f2d8eae79db09860782560e8833aeb1f20fac8aecfe22f6880637 46bdaa64-fb11-4de2-b318-2b266a7391e0 Supplemental data Public 41467_2023_44631_MOESM9_ESM.mov 38830378 video/quicktime cf98a6ef805e9eaeb5f2027b4a916051c8cd1982355efa24594f2deee63a8164 df98216d-a1a8-4c08-8c2f-ba0a189da0d9 Supplemental data Public 41467_2023_44631_MOESM10_ESM.mov 62819817 video/quicktime 9aadec72b4c83d17f297e81b03f65edadaa81df652d43a857dc6cdabea774bce eb827f36-ff89-4796-825a-ea4281c3d0f0 Supplemental data Public 41467_2023_44631_MOESM11_ESM.xlsx 24245 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet db80a5f4698094bf76ab0d6388e51e245ada9b887a717fb5d2fd3a2dbf7ca191 30a5b66a-843a-49dd-8eb8-d39d076d5717 Supplemental data Public 41467_2023_44631_MOESM13_ESM.xlsx 10036773 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 2de137988c0097e21d127efcbe418cd130cb6ece7d8f99160e1db93d02714cc9 openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

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Sustained rhoptry docking and discharge requires Toxoplasma gondii intraconoidal microtubule-associated proteins	Nature communications			2024	349	107

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Delgado Betancourt, Estefania