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

Nicolas Dos Santos Pacheco, Albert Tell i Puig, Amandine Guérin, Matthew Martinez, Bohumil Maco, Nicolò Tosetti, Estefanía Delgado-Betancourt, Matteo Lunghi, Boris Striepen, Yi-Wei Chang () and Dominique Soldati-Favre ()
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Nicolas Dos Santos Pacheco: University of Geneva
Albert Tell i Puig: University of Geneva
Amandine Guérin: University of Pennsylvania
Matthew Martinez: University of Pennsylvania
Bohumil Maco: University of Geneva
Nicolò Tosetti: University of Geneva
Estefanía Delgado-Betancourt: University of Geneva
Matteo Lunghi: University of Geneva
Boris Striepen: University of Pennsylvania
Yi-Wei Chang: University of Pennsylvania
Dominique Soldati-Favre: University of Geneva

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-023-44631-y

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