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An apical membrane complex for triggering rhoptry exocytosis and invasion in Toxoplasma

Sparvoli, Daniela and Delabre, Jason and Penarete-Vargas, Diana Marcela and Kumar Mageswaran, Shrawan and Tsypin, Lev M. and Heckendorn, Justine and Theveny, Liam and Maynadier, Marjorie and Mendonça Cova, Marta and Berry-Sterkers, Laurence and Guérin, Amandine and Dubremetz, Jean-François and Urbach, Serge and Striepen, Boris and Turkewitz, Aaron P. and Chang, Yi‐Wei and Lebrun, Maryse (2022) An apical membrane complex for triggering rhoptry exocytosis and invasion in Toxoplasma. EMBO Journal, 41 (22). Art. No. e111158. ISSN 0261-4189. doi:10.15252/embj.2022111158. https://resolver.caltech.edu/CaltechAUTHORS:20221024-125854800.31

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Abstract

Apicomplexan parasites possess secretory organelles called rhoptries that undergo regulated exocytosis upon contact with the host. This process is essential for the parasitic lifestyle of these pathogens and relies on an exocytic machinery sharing structural features and molecular components with free-living ciliates. However, how the parasites coordinate exocytosis with host interaction is unknown. Here, we performed a Tetrahymena-based transcriptomic screen to uncover novel exocytic factors in Ciliata and conserved in Apicomplexa. We identified membrane-bound proteins, named CRMPs, forming part of a large complex essential for rhoptry secretion and invasion in Toxoplasma. Using cutting-edge imaging tools, including expansion microscopy and cryo-electron tomography, we show that, unlike previously described rhoptry exocytic factors, TgCRMPs are not required for the assembly of the rhoptry secretion machinery and only transiently associate with the exocytic site—prior to the invasion. CRMPs and their partners contain putative host cell-binding domains, and CRMPa shares similarities with GPCR proteins. Collectively our data imply that the CRMP complex acts as a host–molecular sensor to ensure that rhoptry exocytosis occurs when the parasite contacts the host cell.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.15252/embj.2022111158DOIArticle
ORCID:
AuthorORCID
Sparvoli, Daniela0000-0002-5992-3753
Tsypin, Lev M.0000-0002-0642-8468
Theveny, Liam0000-0002-6292-8408
Maynadier, Marjorie0000-0002-1825-3095
Mendonça Cova, Marta0000-0001-6727-248X
Berry-Sterkers, Laurence0000-0002-8150-7860
Guérin, Amandine0000-0001-8307-5099
Dubremetz, Jean-François0000-0002-1362-9110
Urbach, Serge0000-0001-8663-2006
Striepen, Boris0000-0002-7426-432X
Turkewitz, Aaron P.0000-0003-3531-5806
Chang, Yi‐Wei0000-0003-2391-473X
Lebrun, Maryse0000-0002-6292-8408
Additional Information:We thank Sebastian Lourido for the pU6-Universal plasmid, Dominique Soldati-Favre for providing the anti-ARM (ARO) antibodies and pLinker-2xTy-DHFR plasmid, Nicolas Dos Santos Pacheco for helping in setting up the Ultrastructure Expansion Microscopy, Anita Koshy for the toxofilin-Cre plasmid, and Helen Blau's lab for the Cre reporter DSred cell line. We thank Veronique Richard and Frank Godiard of the MEA platform, University of Montpellier, for their assistance with electron microscopy and Pilar Ruga Fahy of the Pôle Facultaire de Microscopie Ultrastructurale, in Geneva for the preparation of freeze-fracture replicas. We are also grateful to Elodie Jublanc, Vicky Diakou, and the imaging facility MRI at the University of Montpellier, part of the national infrastructure France-BioImaging supported by the French National Research Agency (ANR-10-INBS-04, «Investments for the future»), and Christophe Duperray of the MRI-Cytometry at the Institute for Regenerative Medicine and Biotherapy for their assistance and technical support. Mass spectrometry experiments were carried out using the facilities of the Montpellier Proteomics Platform (PPM, BioCampus Montpellier). We thank Stefan Steimle for his technical assistance with the Krios G3i cryogenic electron microscope; the Singh Center for Nanotechnology and the Beckman Center for Cryogenic Electron Microscopy at the University of Pennsylvania for hosting and supporting the use of the Titan Krios. Dr Maryse Lebrun is an INSERM researcher. This work was supported by the Laboratoire d'Excellence (LabEx) (ParaFrap ANR-11-LABX-0024), and European Research Council (ERC advanced grant number 833309 KissAndSpitRhoptry) to M.L.; by the FACCTS (France and Chicago Collaborating in the Sciences) to A.P.T. and M.L.; by NIH GM105783 to A.P.T.; by a David and Lucile Packard Fellowship for Science and Engineering (2019-69645) and a Pennsylvania Department of Health FY19 Health Research Formula Fund to Y.-W.C; and by NIH R01 AI112427 to B.S. D.S. and M.M.C. are supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program under Grant agreement no. 833309 to M.L.
Funders:
Funding AgencyGrant Number
Agence Nationale de la Recherche (ANR)ANR-11-LABX‐0024
David and Lucile Packard Foundation2019-69645
European Research Council (ERC)833309
NIHGM105783
NIHR01 AI112427
Pennsylvania Department of HealthUNSPECIFIED
Issue or Number:22
DOI:10.15252/embj.2022111158
Record Number:CaltechAUTHORS:20221024-125854800.31
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20221024-125854800.31
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:117560
Collection:CaltechAUTHORS
Deposited By: Research Services Depository
Deposited On:01 Nov 2022 20:24
Last Modified:25 Jan 2023 20:12

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