Cellular movement is key to life and in the case of intracellular parasites, provides a vital mechanism to gain access to the protected niche they require. The parasite Toxoplasma gondii is a model for a group of parasites called apicomplexans, which move by an actin-dependent process referred to as gliding motility. This form of motility is distinct from that used by ciliated or flagellated cells, and from the crawling behavior of amoeba and many mammalian cells.
A new paper demonstrates that the normally highly conserved protein actin is divergent in these parasites and that it displays unusual kinetic properties that result in formation of short unstable filaments, in contrast to the highly stable nature of mammalian actin. The findings reveal that the short dynamic nature of parasite actins is due to a small number of amino acid differences that affect stability of the filament. These properties are essential to normal parasite motility since reversion of these residues to match those seen in mammalian cells was detrimental to gliding movement. The dependence of parasites on rapid turnover of highly unstable actins renders them extremely sensitive to toxins that stabilize actin filaments, thus providing a potential target for development of specific intervention.
Evolutionarily Divergent, Unstable Filamentous Actin Is Essential for Gliding Motility in Apicomplexan Parasites. (2011) PLoS Pathog 7(10): e1002280. doi:10.1371/journal.ppat.1002280
Apicomplexan parasites rely on a novel form of actin-based motility called gliding, which depends on parasite actin polymerization, to migrate through their hosts and invade cells. However, parasite actins are divergent both in sequence and function and only form short, unstable filaments in contrast to the stability of conventional actin filaments. The molecular basis for parasite actin filament instability and its relationship to gliding motility remain unresolved. We demonstrate that recombinant Toxoplasma (TgACTI) and Plasmodium (PfACTI and PfACTII) actins polymerized into very short filaments in vitro but were induced to form long, stable filaments by addition of equimolar levels of phalloidin. Parasite actins contain a conserved phalloidin-binding site as determined by molecular modeling and computational docking, yet vary in several residues that are predicted to impact filament stability. In particular, two residues were identified that form intermolecular contacts between different protomers in conventional actin filaments and these residues showed non-conservative differences in apicomplexan parasites. Substitution of divergent residues found in TgACTI with those from mammalian actin resulted in formation of longer, more stable filaments in vitro. Expression of these stabilized actins in T. gondii increased sensitivity to the actin-stabilizing compound jasplakinolide and disrupted normal gliding motility in the absence of treatment. These results identify the molecular basis for short, dynamic filaments in apicomplexan parasites and demonstrate that inherent instability of parasite actin filaments is a critical adaptation for gliding motility.