Toxoplasma Parasite Twisting Motion Mechanically Induces Host Cell Membrane Fission to Complete Invasion within a Protective Vacuole

Cell Host Microbe. 2018 Jul 11;24(1):81-96.e5. doi: 10.1016/j.chom.2018.06.003. Epub 2018 Jun 28.

Abstract

To invade cells, the parasite Toxoplasma gondii injects a multi-unit nanodevice into the target cell plasma membrane (PM). The core nanodevice, which is composed of the RhOptry Neck (RON) protein complex, connects Toxoplasma and host cell through a circular tight junction (TJ). We now report that this RON nanodevice mechanically promotes membrane scission at the TJ-PM interface, directing a physical rotation driven by the parasite twisting motion that enables the budding parasitophorous vacuole (PV) to seal and separate from the host cell PM as a bona fide subcellular Toxoplasma-loaded PV. Mechanically impairing the process induces swelling of the budding PV and death of the parasite but not host cell. Moreover, this study reveals that the parasite nanodevice functions as a molecular trigger to promote PV membrane remodeling and rapid onset of T. gondii to intracellular lifestyle.

Keywords: cellular microbiology; high-speed live imaging; host cell invasion; human cell Alix; human cell dynamins; mechanical force; membrane dynamics; membrane fission; osmotic swelling; protozoan parasite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism*
  • Female
  • Fibroblasts / parasitology*
  • Fibroblasts / ultrastructure
  • Host-Parasite Interactions
  • Humans
  • Mice
  • Mice, Transgenic
  • Optical Imaging
  • Patch-Clamp Techniques
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Rotation
  • Tight Junctions / metabolism
  • Toxoplasma / genetics
  • Toxoplasma / pathogenicity*
  • Vacuoles / parasitology*

Substances

  • Protozoan Proteins
  • rhoptry neck protein 2, Toxoplasma gondii