Conoid extrusion regulates glideosome assembly to control motility and invasion in Apicomplexa

SUMMARY 

Members of Apicomplexa are defined by apical cytoskeletal structures and secretory organelles, tailored for motility, invasion and egress. Gliding is powered by actomyosin-dependent rearward translocation of apically secreted transmembrane adhesins. In the human parasite Toxoplasma gondii, the conoid, composed of tubulin fibres and preconoidal rings (PCRs), is a dynamic organelle of undefined function. Here, using ultrastructure expansion microscopy, the research group led by GCIR member Professor Dominique Soldati-Favre, established that PCRs serve as a hub for glideosome components including Formin1. They also identified components of the PCRs conserved in Apicomplexa, Pcr4 and Pcr5, that contain B-box zinc-finger domains, assemble in heterodimer and are essential for the formation of the structure. The fitness conferring Pcr6 tethers the PCRs to the cone of tubulin fibres. F-actin produced by Formin1 is used by Myosin H to generate the force for conoid extrusion which directs the flux of F-actin to the pellicular space, serving as gatekeeper to control parasite motility.

This work was supported by the Swiss National Foundation, the Novartis Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation programme.

Full article: https://www.nature.com/articles/s41564-022-01212-x

Why is this article important?

During infection, Toxoplasma gondii glides along the host cell surface, attaches to, and then rapidly invades the host cell. However, immediately after invasion, the parasite becomes non-motile to avoid premature rupture of the host cell, thus allowing multiple rounds of replication within the same cell and optimal utilisation of host resources.

How does the parasite regulate its motility? Professor Soldati-Favre's team used ultrastructure expansion microscopy (U-ExM) to map at nanoscale resolution the location of known key invasion factors as well as novel proteins to the conoid, a unique dynamic organelle of the parasite.  The extrusion and retraction of the conoid are indispensable for motility and invasion. They identified new components of the conoid and were able to postulate a model to explain the role of conoid dynamics in controlling parasite motility. This mechanism is of vital importance for understanding how parasite egress and host cell invasion are controlled.

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