From force generation to host cell attachment: new function of the acto-MyoA motor complex in Toxoplasma gondii tachyzoites

Abstract:

The Apicomplexan parasite Toxoplasma gondii is considered an extremely successful pathogen for its capacity to invade virtually any nucleated cell. Host cell invasion is an active process thought to be driven by the same acto-myosin machinery that drives gliding motility. The current model suggests that at the core of the complex is MyoA, a small unconventional class XIVa myosin, which, together with its molecular partner myosin light chain 1 (MLC1), produces mechanical force on short actin (ACT1) filaments to power gliding and invasion. However, efficient conditional removal of the key components of the acto-MyoA motor complex indicated that although these proteins were important, they were not essential for motility or invasion. Some plausible explanations of this surprising finding were: probable redundancy among motor complex proteins, presence of residual protein in the conditional mutant lines, and/or compensatory mechanisms for driving these essential steps of the T. gondii life cycle. Considering these hypotheses, and given that T. gondii encodes for 11 myosins and 7 myosin light chains, this study focused on different possibilities upon MyoA and MLC1 depletion, Therefore, overlapping subcellular localisations and functions had to be considered. Due to its structural similarity, and that it shares molecular partners with MyoA, myosin C (MyoC) was the first candidate considered to compensate for MyoA function in the myoA KO. In fact, a myoA/B/C KO was unable to grow in in vitro conditions due to a detrimental egress phenotype, although it could still glide and invade. Here, the mlc1 KO, myoB/C/mlc1 KO, and a set of MyoC …

Año de publicación:

2018

Keywords:

Fuente:

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