Toxoplasma gondii motility and host cell invasiveness are drastically impaired by jasplakinolide, a cyclic peptide stabilizing F-actin

Actin polymerization and actin-myosin coupling activity most likely provide the driving force that the protozoan parasite Toxoplasma gondii has to exe rt to propulse itself during gliding and host cell entry. Nevertheless, lit tle information is available on T. gondii tachyzoite actin dynamics, and in particular, the presence of actin filaments remains largely uncharacterize d. Here, we report chat the marine sponge peptide jasplakinolide, known to bind to filamentous actin, does indeed stabilize a pool of a parasite deter gent-insoluble actin. This pool is likely to be formed by a dynamic assembl ed actin complex: first, it is competent for assembly/disassembly and secon dly, it is sensitive to nucleotide phosphate concentration. In addition, T. gondii tachyzoites contain molecules which inhibit actin assembly and dest abilize actin filaments. Thus, these activities could account for the remar kably low amount of the myosin-containing F-actin pool we describe here. Fu rthermore, when parasites are treated with cell-permeant jasplakinolide, th ey display a significant loss of both motility and host cell invasiveness. These data suggest that in vivo, the detergent-insoluble pool of actin is d ynamic. (C) Elsevier, Paris.