From nucleation to capping: The lifecycle of an actin filament in Toxoplasma gondii gliding

Toxoplasma gondii is an obligate intracellular apicomplexan parasite whose motility, host cell invasion, and egress are powered by a unique actomyosin system. Unlike canonical actins that form stable filaments, T. gondii actin (TgACT1) is highly dynamic, existing predominantly in a monomeric state. This review traces the lifecycle of TgACT1, from nucleation to capping, to elucidate how the parasite harnesses rapid cytoskeletal turnover for gliding motility. This review discusses how TgACT1's intrinsic properties-including isodesmic polymerization, rapid subunit turnover, and specific amino acid substitutions that confer instability-are complemented by a minimal set of TgACT1-binding proteins (e.g., formins, TgPRF, toxofilin, ADF) to maintain a readily available pool of polymerization-competent monomers. The force for motility is generated by the glideosome, a specialized motor complex where myosin A walks along short, dynamic filaments, translocating adhesins rearward to propel the parasite. Finally, the therapeutic potential of targeting this essential and divergent system is discussed, highlighting the druggability of TgACT1 and the immunogenic properties of key regulators. Understanding the molecular mechanisms of TgACT1 dynamics reveals vulnerabilities that could be exploited for novel anti-parasitic strategies.