A Toxoplasma Gondii Protein With Homology to Intracellular Type Na⁺/H⁺ Exchangers Is Important for Osmoregulation and Invasion

Exp Cell Res. 2011 Jun 10;317(10):1382-96. doi: 10.1016/j.yexcr.2011.03.020. Epub 2011 Apr 9.

Abstract

The obligate intracellular parasite Toxoplasma gondii is exposed to a variety of physiological conditions while propagating in an infected organism. The mechanisms by which Toxoplasma overcomes these dramatic changes in its environment are not known. In yeast and plants, ion detoxification and osmotic regulation are controlled by vacuolar compartments. A novel compartment named the plant-like vacuole or vacuolar compartment (PLV/VAC) has recently been described in T.gondii, which could potentially protect extracellular tachyzoites against salt and other ionic stresses. Here, we report the molecular characterization of the vacuolar type Na(+)/H(+) exchanger in T. gondii, TgNHE3, and its co-localization with the PLV/VAC proton-pyrophosphatase (TgVP1). We have created a TgNHE3 knockout strain, which is more sensitive to hyperosmotic shock and toxic levels of sodium, possesses a higher intracellular Ca(2+) concentration [Ca(2+)](i), and exhibits a reduced host invasion efficiency. The defect in invasion correlates with a measurable reduction in the secretion of the adhesin TgMIC2. Overall, our results suggest that the PLV/VAC has functions analogous to those of the vacuolar compartments of plants and yeasts, providing the parasite with a mechanism to resist ionic fluctuations and, potentially, regulate protein trafficking.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Blotting, Western
  • Calcium / metabolism
  • Cell Adhesion
  • Cell Movement*
  • Cell Proliferation
  • Cloning, Molecular
  • Fibroblasts
  • Fluorescent Antibody Technique
  • Guinea Pigs
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Protein Transport
  • Protons
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Protozoan Proteins / metabolism*
  • Pyrophosphatases / genetics
  • Pyrophosphatases / metabolism
  • Sequence Homology, Amino Acid
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / immunology
  • Sodium-Hydrogen Exchangers / metabolism*
  • Toxoplasma / genetics
  • Toxoplasma / growth & development
  • Toxoplasma / metabolism*
  • Toxoplasmosis
  • Vacuoles / metabolism*
  • Water-Electrolyte Balance / physiology*

Substances

  • NHE3 protein, Toxoplasma gondii
  • Protons
  • Protozoan Proteins
  • Sodium-Hydrogen Exchangers
  • Pyrophosphatases
  • Calcium