The Toxoplasma Acto-MyoA Motor Complex Is Important but Not Essential for Gliding Motility and Host Cell Invasion

Abstract

Apicomplexan parasites are thought to actively invade the host cell by gliding motility. This movement is powered by the parasite's own actomyosin system, and depends on the regulated polymerisation and depolymerisation of actin to generate the force for gliding and host cell penetration. Recent studies demonstrated that Toxoplasma gondii can invade the host cell in the absence of several core components of the invasion machinery, such as the motor protein myosin A (MyoA), the microneme proteins MIC2 and AMA1 and actin, indicating the presence of alternative invasion mechanisms. Here the roles of MyoA, MLC1, GAP45 and Act1, core components of the gliding machinery, are re-dissected in detail. Although important roles of these components for gliding motility and host cell invasion are verified, mutant parasites remain invasive and do not show a block of gliding motility, suggesting that other mechanisms must be in place to enable the parasite to move and invade the host cell. A novel, hypothetical model for parasite gliding motility and invasion is presented based on osmotic forces generated in the cytosol of the parasite that are converted into motility.

Gliding motility powers invasion and egress in Apicomplexa

“…4a). The conditional excision of T. gondii actin (TgACT1) severely compromised motility, invasion and egress 23,24 , although the parasites could still be propagated for several days, which raised the possibility of the coexistence of an actin-independent mechanism of motility 25,26 . Nature Reviews | Microbiology .…”

“…The conserved, short single-headed myosin heavy chain myosin A (MYOA), was then identified in T. gondii as the motor that was able to generate the rearward traction force necessary for motility, entry into, and egress from, host cells 48 . The composition and molecular details of the glideosome have been elucidated in more detail and discovered, respectively [49][50][51][52] , and the importance of the glideosome in motility and invasion has been assessed further 23,25,26,53,54 (Supplementary information S6 (table)). …”

Functions of myosin motors tailored for parasitism

“…Conditional DiCre-dependent excision of the genes coding for the core components of the glideosome, such as TgMyoA, TgGAP40, TgGAP45, TgGAP50, TgMLC1 and TgACT1 have been generated using notably the geneswap strategy [45,46]. From this list only parasites lacking TgMyoA have been cloned, suggesting that other myosins might contribute and compensate for the absence of this motor in the glideosome function or that a myosin-independent process sustains residual invasion including the participation of host cell membrane dynamics [46,47 ].…”

“…From this list only parasites lacking TgMyoA have been cloned, suggesting that other myosins might contribute and compensate for the absence of this motor in the glideosome function or that a myosin-independent process sustains residual invasion including the participation of host cell membrane dynamics [46,47 ]. Noteworthy a combined deletion of TgMyoA and TgMyoB/ C could not be isolated [46] and TgMyoC assembles into a glideosome that shares several components with the TgMyoA-glideosome, that is, the myosin light chains, TgGAP50 and TgGAP40 (Figures 2-4) [48]. Instead of TgGAP45, TgGAP80 recruits TgMyoC to the basal polar ring and assembles the TgMyoC-glideosome [48].…”

Advantages and disadvantages of conditional systems for characterization of essential genes in Toxoplasma gondii

“…1A-C) Egarter et al 2014); at a transcriptional level, using the Tet-transactivator system ( Fig. 1D and E) (Meissner et al 2002); and at a protein level, using the ddFKBP-system to over-express the MyoA-tail ( Fig.…”