Apicomplexan F-actin is required for efficient nuclear entry during host cell invasion

EMBO Rep. 2019 Dec 5;20(12):e48896. doi: 10.15252/embr.201948896. Epub 2019 Oct 4.

Abstract

The obligate intracellular parasites Toxoplasma gondii and Plasmodium spp. invade host cells by injecting a protein complex into the membrane of the targeted cell that bridges the two cells through the assembly of a ring-like junction. This circular junction stretches while the parasites apply a traction force to pass through, a step that typically concurs with transient constriction of the parasite body. Here we analyse F-actin dynamics during host cell invasion. Super-resolution microscopy and real-time imaging highlighted an F-actin pool at the apex of pre-invading parasite, an F-actin ring at the junction area during invasion but also networks of perinuclear and posteriorly localised F-actin. Mutant parasites with dysfunctional acto-myosin showed significant decrease of junctional and perinuclear F-actin and are coincidently affected in nuclear passage through the junction. We propose that the F-actin machinery eases nuclear passage by stabilising the junction and pushing the nucleus through the constriction. Our analysis suggests that the junction opposes resistance to the passage of the parasite's nucleus and provides the first evidence for a dual contribution of actin-forces during host cell invasion by apicomplexan parasites.

Keywords: Apicomplexa; actin; host cell invasion; myosin; nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / physiology*
  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Cell Nucleus / parasitology
  • Cell Nucleus / physiology
  • Cells, Cultured
  • Gene Knockout Techniques
  • Host-Parasite Interactions / physiology*
  • Humans
  • Merozoites / genetics
  • Merozoites / pathogenicity
  • Merozoites / physiology
  • Models, Biological
  • Mutation
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / pathogenicity*
  • Plasmodium falciparum / physiology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / physiology*
  • Signal Transduction
  • Toxoplasma / genetics
  • Toxoplasma / parasitology*
  • Toxoplasma / pathogenicity*
  • Virulence / physiology

Substances

  • Actins
  • Protozoan Proteins