Architecture of the Toxoplasma gondii apical polar ring and its role in gliding motility and invasion

Summary

In Toxoplasma gondii, the conoid comprises a cone with spiraling tubulin fibers, preconoidal rings, and intraconoidal microtubules. This dynamic organelle undergoes extension and retraction through the apical polar ring (APR) during egress, gliding, and invasion. The forces involved in conoid extrusion are beginning to be understood, and its role in directing F-actin flux to the pellicular space, thereby controlling parasite motility, has been proposed. However, the contribution of the APR and its interactions with the conoid remain unclear. To gain insight into the APR architecture, ultrastructure expansion microscopy was applied to pinpoint known and newly identified APR proteins (APR2 to APR7). The results of this work, led by Pr Dominique Soldati-Favre, revealed that the APR is constructed as a fixed multilayered structure. Notably, conditional depletion of APR2 resulted in significant impairments in motility and invasion. Electron microscopy and cryoelectron tomography revealed that depletion of APR2 alters APR integrity, affecting conoid extrusion and causing cytosolic leakage of F-actin. These findings implicate the APR structure in directing the apico-basal flux of F-actin to regulate parasite motility and invasion.

Full article: https://www.pnas.org/doi/10.1073/pnas.2416602121

What did the authors discover and why is it important to study toxoplasmosis?

Obligate intracellular parasites of the Apicomplexa phylum rely on the apical complex for motility and host cell invasion. Researchers identified the apical polar ring (APR) and its protein APR2 as critical for regulating actin flow, a key process for Toxoplasma gondii motility. Without APR2, actin flow becomes misdirected, disrupting the parasite's movement and invasion capabilities. Advanced imaging mapped the APR’s architecture and its role in positioning the conoid, a dynamic organelle that extends and retracts to control motility. These insights could inform strategies to combat parasitic infections.

Toxoplasma gondii is the intracellular parasite that causes Toxoplasmosis. Toxoplasmosis has significant health, veterinary, and public health implications.

Global prevalence

Up to one-third of the global population is infected with Toxoplasma gondii, making it one of the most widespread parasitic infections worldwide.

Vulnerable populations

While often asymptomatic in healthy individuals, toxoplasmosis can cause severe complications in immunocompromised people (e.g., those with HIV or undergoing chemotherapy) and pregnant women. Congenital toxoplasmosis may result in miscarriages, stillbirths, or lifelong neurological and developmental issues in infants.

Economic and agricultural impact

Toxoplasmosis affects livestock, causing abortions in animals like sheep and goats, leading to significant economic losses. The parasite poses a food safety risk through transmission in undercooked meat.

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