MyoD

TgMyoD is a class XIV myosin of Toxoplasma gondii that possesses in vitro motor activity kinetically comparable to the glideosome motor TgMyoA, yet is functionally distinct in its cellular role (PMID:16470333). Genetic disruption demonstrates it is dispensable for tachyzoite gliding motility, host cell invasion, egress, and virulence, a lack of phenotype explained by its predominant expression in bradyzoites, which points to a motor function restricted to the cyst-forming stage (PMID:16470333). TgMyoD forms a complex with the light chain MLC2, which binds via its calmodulin-like domain and anchors the motor to the plasma membrane through an N-terminal extension likely modified by palmitoylation — a localization distinct from the inner membrane complex positioning of the MyoA-MLC1 motor (PMID:21143563). Beyond this motor-light chain complex and its stage-restricted expression, no further mechanistic detail on TgMyoD's cellular function has been characterized in the available corpus.

1. 2006 High

   Whether TgMyoD is a functional motor and whether it contributes to the actinomyosin-driven motility that powers tachyzoite invasion was unknown; kinetic and knockout analysis established that it is a bona fide motor yet dispensable for the tachyzoite lytic cycle.

   Evidence Transient kinetic biophysical assays plus double homologous recombination knockout scored for gliding, invasion, egress, and mouse virulence, with stage-specific expression analysis

   PMID:16470333

   Open questions at the time

   • The specific cargo, track, or cellular process TgMyoD drives in bradyzoites was not identified
   • No bradyzoite-stage functional assay directly tested a phenotype for TgMyoD
   • The structural basis of its motor activity was not resolved
2. 2011 Medium

   The light chain partner and subcellular positioning of the TgMyoD motor were undefined; identifying MLC2 and mapping its plasma-membrane anchoring established a MyoD-MLC2 complex distinct from the IMC-localized MyoA-MLC1 glideosome.

   Evidence Subcellular localization by immunofluorescence/fractionation, molecular modeling, and identification of MLC2 as the MyoD-associated light chain via co-localization and interaction studies

   PMID:21143563

   Open questions at the time

   • Full reconstitution and mutagenesis of the MyoD-MLC2 interface were not described
   • Palmitoylation of the MLC2 N-terminal extension was inferred rather than directly demonstrated
   • Functional consequence of plasma-membrane anchoring for the motor was not tested

• The physiological substrate and cellular role of the plasma-membrane-anchored MyoD-MLC2 motor within the cyst-forming bradyzoite stage remain unresolved.
• No bradyzoite-specific function has been assigned to TgMyoD
• The cargo moved and the biological process served by plasma-membrane anchoring are unknown