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

50 Citations (Scopus)

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

Fingerprint

Sodium-Hydrogen Antiporter
Ionophores
Toxoplasma
Calcimycin
Parasites
Calcium
Amiloride
Eukaryotic Cells
Protons
Homeostasis
Cell Membrane
Genes

Keywords

  • Calcium
  • Egress
  • Ionophore
  • NHE
  • Toxoplasma

ASJC Scopus subject areas

  • Cell Biology

Cite this

Ionophore-resistant mutant of Toxoplasma gondii reveals involvement of a sodium/hydrogen exchanger in calcium regulation. / Arrizabalaga, Gustavo; Ruiz, Felix; Moreno, Silvia; Boothroyd, John C.

In: Journal of Cell Biology, Vol. 165, No. 5, 07.06.2004, p. 653-662.

Research output: Contribution to journalArticle

@article{f075d28707854680a4d87b384894fe2b,
title = "Ionophore-resistant mutant of Toxoplasma gondii reveals involvement of a sodium/hydrogen exchanger in calcium regulation",
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.",
keywords = "Calcium, Egress, Ionophore, NHE, Toxoplasma",
author = "Gustavo Arrizabalaga and Felix Ruiz and Silvia Moreno and Boothroyd, {John C.}",
year = "2004",
month = "6",
day = "7",
doi = "10.1083/jcb.200309097",
language = "English (US)",
volume = "165",
pages = "653--662",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "5",

}

TY - JOUR

T1 - Ionophore-resistant mutant of Toxoplasma gondii reveals involvement of a sodium/hydrogen exchanger in calcium regulation

AU - Arrizabalaga, Gustavo

AU - Ruiz, Felix

AU - Moreno, Silvia

AU - Boothroyd, John C.

PY - 2004/6/7

Y1 - 2004/6/7

N2 - 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.

AB - 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.

KW - Calcium

KW - Egress

KW - Ionophore

KW - NHE

KW - Toxoplasma

UR - http://www.scopus.com/inward/record.url?scp=2942633901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942633901&partnerID=8YFLogxK

U2 - 10.1083/jcb.200309097

DO - 10.1083/jcb.200309097

M3 - Article

C2 - 15173192

AN - SCOPUS:2942633901

VL - 165

SP - 653

EP - 662

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

ER -