Ionophore-resistant mutant of Toxoplasma gondii reveals involvement of a sodium/hydrogen exchanger in calcium regulation

Gustavo Arrizabalaga, Felix Ruiz, Silvia Moreno, John C. Boothroyd

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Calcium is a critical mediator of many intracellular processes in eukaryotic cells. In the obligate intracellular parasite Toxoplasma gondii, for example, a rise in [Ca2+] is associated with significant morphological changes and rapid egress from host cells. To understand the mechanisms behind such dramatic effects, we isolated a mutant that is altered in its responses to the Ca2+ ionophore A23187 and found the affected gene encodes a homologue of Na+/H+ exchangers (NHEs) located on the parasite's plasma membrane. We show that in the absence of TgNHE1, Toxoplasma is resistant to ionophore-induced egress and extracellular death and amiloride-induced proton efflux inhibition. In addition, the mutant has increased levels of intracellular Ca2+, which explains its decreased sensitivity to A23187. These results provide direct genetic evidence of a role for NHE1 in Ca2+ homeostasis and important insight into how this ubiquitous pathogen senses and responds to changes in its environment.

Original languageEnglish (US)
Pages (from-to)653-662
Number of pages10
JournalJournal of Cell Biology
Volume165
Issue number5
DOIs
StatePublished - Jun 7 2004
Externally publishedYes

Keywords

  • Calcium
  • Egress
  • Ionophore
  • NHE
  • Toxoplasma

ASJC Scopus subject areas

  • Cell Biology

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