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Tang, Qing

Microbiology and Molecular Genetics

2013

PhD

Toxoplasma gondii (T.gondii) belongs to the apicomplexan phylum of parasites that cause devastating infectious diseases in both humans and animals. As an obligate intracellular parasite, T.gondii relies on its substrate-dependent gliding motility to drive host cell invasion and egress. The machinery that is critical for these cellular processes comprises at least 6 components assembled into the T.gondii myosin A (TgMyoA) motor complex at the parasite cell periphery. TgMyoA belongs to class XIV myosins which are only found in the apicomplexans. As a founding member of this myosin family, TgMyoA has unique features as a single-headed, fast, unconventional myosin. Despite its vital roles in the T.gondii lytic cycle, TgMyoA is poorly understood in terms of how it is regulated.
Phosphoproteomics studies have revealed prevalent phosphorylation events on multiple components of the TgMyoA motor complex including TgMyoA. A recently identified invasion/motility enhancer molecule preferentially increased TgMyoA phosphorylation among all the components in the motor complex. The enhancement of TgMyoA phosphorylation is calcium dependent, and interestingly, calcium ionophore (A23187) can also enhance TgMyoA phosphorylation. Introducing alanine mutations at phosphorylated residues on TgMyoA abolished TgMyoAphosphorylation and conferred triggered egress. Phospho-mimetic mutations on the same sites restored the cellular response to enhancer and A23187, providing evidence that phosphorylation on TgMyoA promotes TgMyoA function upon stimulation.