Calcium entry in Toxoplasma gondii and its enhancing effect of invasion-linked traits

J Biol Chem. 2014 Jul 11;289(28):19637-47. doi: 10.1074/jbc.M114.565390. Epub 2014 May 27.

Abstract

During invasion and egress from their host cells, Apicomplexan parasites face sharp changes in the surrounding calcium ion (Ca(2+)) concentration. Our work with Toxoplasma gondii provides evidence for Ca(2+) influx from the extracellular milieu leading to cytosolic Ca(2+) increase and enhancement of virulence traits, such as gliding motility, conoid extrusion, microneme secretion, and host cell invasion. Assays of Mn(2+) and Ba(2+) uptake do not support a canonical store-regulated Ca(2+) entry mechanism. Ca(2+) entry was blocked by the L-type Ca(2+) channel inhibitor nifedipine and stimulated by the increase in cytosolic Ca(2+) and by the specific L-type Ca(2+) channel agonist Bay K-8644. Our results demonstrate that Ca(2+) entry is critical for parasite virulence. We propose a regulated Ca(2+) entry mechanism activated by cytosolic Ca(2+) that has an enhancing effect on invasion-linked traits.

Keywords: Calcium; Cell Invasion; Conoid Extrusion; Fluorescence; Gliding Motility; Nifedipine; Parasite; Protozoan; Signaling; Toxoplasma gondii.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Barium / metabolism
  • Calcium / metabolism*
  • Calcium Channel Agonists / pharmacology
  • Calcium Channels, L-Type / metabolism*
  • Humans
  • Manganese / metabolism
  • Protozoan Proteins / antagonists & inhibitors
  • Protozoan Proteins / metabolism*
  • Quantitative Trait Loci / physiology*
  • Toxoplasma / metabolism*
  • Toxoplasma / pathogenicity*
  • Toxoplasmosis / metabolism

Substances

  • Calcium Channel Agonists
  • Calcium Channels, L-Type
  • Protozoan Proteins
  • Barium
  • Manganese
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Calcium