Toxoplasma gondii rhoptry discharge factor 3 is essential for invasion and microtubule-associated vesicle biogenesis

Focused ion beam–scanning electron microscopy-based three-dimensional reconstruction of a rosette composed of 16 Toxoplasma gondii tachyzoites in a parasitophorous vacuole. Grey, nucleus; green, apicoplast; blue, parasite plasma membrane; black, conoid; yellow rhoptry bulb; red rhoptry neck. ©Bohumil MACO/UNIGE

SUMMARY

Rhoptries are specialized secretory organelles conserved across the Apicomplexa phylum, essential for host cell invasion and critical for subverting of host cellular and immune functions. They contain proteins and membranous materials injected directly into the host cells, participating in parasitophorous vacuole formation. Toxoplasma gondii tachyzoites harbor 8 to 12 rhoptries, 2 of which are docked to an apical vesicle (AV), a central element associated with a rhoptry secretory apparatus prior to injection into the host cell. This parasite is also equipped with 5 to 6 microtubule-associated vesicles, presumably serving as AV replenishment for iterative rhoptry discharge. Here, we characterized a rhoptry protein, rhoptry discharge factor 3 (RDF3), crucial for rhoptry discharge and invasion. RDF3 enters the secretory pathway, localizing near the AV and associated with the rhoptry bulb. Upon invasion, RDF3 dynamically delocalizes, suggesting a critical role at the time of rhoptry discharge. Cryo-electron tomography analysis of RDF3-depleted parasites reveals irregularity in microtubule-associated vesicles morphology, presumably impacting on their preparedness to function as an AV. Our findings suggest that RDF3 is priming the microtubule-associated vesicles for rhoptry discharge by a mechanism distinct from the rhoptry secretory apparatus contribution.

Full article: https://doi.org/10.1371/journal.pbio.3002745

WHY IS IT IMPORTANT?

In Toxoplasma gondii, the intracellular parasite that causes toxoplasmosis, rhoptries are essential organelles for invading host cells. The latest publication from Prof. Soldati-Favre's group focuses on RDF3, a protein vital for the parasite's invasion process. RDF3 is required for the proper formation of microtubule-associated vesicles (MVs), which supply the rhoptries during repeated invasion cycles. Depletion of RDF3 disrupts these processes, highlighting its critical role in parasite virulence. Understanding the function of RDF3 could inform strategies to treat T. gondii and related parasite infections.

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