Mol Biol Cell. 2011 Feb 23. [Epub ahead of print]
Actin Depolymerizing Factor controls actin turnover and gliding motility in Toxoplasma gondii
Mehta S, Sibley LD.
Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110.
Apicomplexan parasites rely on actin-based gliding motility to move across the substratum, cross biological barriers, and invade their host cells. Gliding motility depends on polymerization of parasite actin filaments, yet ∼98% of actin is non-filamentous in resting parasites. Previous studies suggest that the lack of actin filaments in the parasite is due to inherent instability, leaving uncertain the role for actin-binding proteins in controlling dynamics. We have previously shown that the single allele of Toxoplasma gondii ADF (TgADF) has strong actin monomer sequestering and weak filament severing activities in vitro. Here we used a conditional knockout strategy to investigate the role of TgADF in vivo. Suppression of TgADF led to accumulation of actin-rich filaments that were detected by immunofluorescence and EM. Parasites deficient in TgADF showed reduced speed of motility, increased aberrant patterns of motion, and inhibition of sustained helical gliding. Lack of TgADF also led to severe defects in entry and egress from host cells, thus blocking infection in vitro. These studies establish that the absence of stable actin structures in the parasite are not simply the result of intrinsic instability, but that TgADF is required for the rapid turnover of parasite actin filaments, gliding motility, and cell invasion.
PMID: 21346192 [PubMed - as supplied by publisher]