Ionophore-resistant Mutant of Toxoplasma Gondii Reveals Involvement of a Sodium/hydrogen Exchanger in Calcium Regulation

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2004 Jun 3

PMID 15173192

Citations 45

Authors

Gustavo Arrizabalaga

Felix Ruiz

Silvia Moreno

John C Boothroyd

Affiliations

Soon will be listed here.

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.

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