Blocking Palmitoylation of Toxoplasma gondii Myosin Light Chain 1 Disrupts Glideosome Composition but Has Little Impact on Parasite Motility

mSphere. 2021 May 19;6(3):e00823-20. doi: 10.1128/mSphere.00823-20.


Toxoplasma gondii is a widespread apicomplexan parasite that causes severe disease in immunocompromised individuals and the developing fetus. Like other apicomplexans, T. gondii uses an unusual form of substrate-dependent gliding motility to invade cells of its hosts and to disseminate throughout the body during infection. It is well established that a myosin motor consisting of a class XIVa heavy chain (TgMyoA) and two light chains (TgMLC1 and TgELC1/2) plays an important role in parasite motility. The ability of the motor to generate force at the parasite periphery is thought to be reliant upon its anchoring and immobilization within a peripheral membrane-bound compartment, the inner membrane complex (IMC). The motor does not insert into the IMC directly; rather, this interaction is believed to be mediated by the binding of TgMLC1 to the IMC-anchored protein, TgGAP45. Therefore, the binding of TgMLC1 to TgGAP45 is considered a key element in the force transduction machinery of the parasite. TgMLC1 is palmitoylated, and we show here that palmitoylation occurs on two N-terminal cysteine residues, C8 and C11. Mutations that block TgMLC1 palmitoylation completely abrogate the binding of TgMLC1 to TgGAP45. Surprisingly, the loss of TgMLC1 binding to TgGAP45 in these mutant parasites has little effect on their ability to initiate or sustain movement. These results question a key tenet of the current model of apicomplexan motility and suggest that our understanding of gliding motility in this important group of human and animal pathogens is not yet complete.IMPORTANCE Gliding motility plays a central role in the life cycle of T. gondii and other apicomplexan parasites. The myosin motor thought to power motility is essential for virulence but distinctly different from the myosins found in humans. Consequently, an understanding of the mechanism(s) underlying parasite motility and the role played by this unusual myosin may reveal points of vulnerability that can be targeted for disease prevention or treatment. We show here that mutations that uncouple the motor from what is thought to be a key structural component of the motility machinery have little impact on parasite motility. This finding runs counter to predictions of the current, widely held "linear motor" model of motility, highlighting the need for further studies to fully understand how apicomplexan parasites generate the forces necessary to move into, out of, and between cells of the hosts they infect.

Keywords: MyoA; Toxoplasma; apicomplexan parasite; motility; myosin; myosin light chain; palmitoylation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Fibroblasts / parasitology
  • Foreskin / cytology
  • Host-Parasite Interactions / physiology
  • Humans
  • Life Cycle Stages
  • Lipoylation*
  • Male
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / genetics
  • Molecular Motor Proteins / chemistry*
  • Molecular Motor Proteins / genetics
  • Molecular Motor Proteins / metabolism
  • Movement
  • Mutation
  • Myosin Light Chains / antagonists & inhibitors*
  • Myosin Light Chains / genetics
  • Protozoan Proteins / antagonists & inhibitors*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Toxoplasma / genetics
  • Toxoplasma / metabolism*


  • Membrane Proteins
  • Molecular Motor Proteins
  • Myosin Light Chains
  • Protozoan Proteins