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An exit exchanger

Toxoplasma need a plasma membrane ion exchanger (right) for a speedy exit.

The protozoan parasite Toxoplasma gondii heads out of its host cell when Ca²⁺ levels peak in its cytoplasm. Now, Arrizabalaga et al. (page 653) find that proper regulation of these Ca²⁺ levels, and thus of Toxoplasma exit, requires a Na⁺/H⁺ exchanger (NHE), suggesting a link between proton and Ca²⁺ regulation.

The increase in Ca²⁺ levels, which can be induced artificially with an ionophore, triggers a series of morphological changes that primes Toxoplasma for both exit and a speedy entrance into a neighboring cell. Death can ensue, however, if the ionophore sticks around while there is no target cell for the parasite to enter; presumably the overstimulated Toxoplasma cannot sustain itself in an activated state.

The authors used this death assay to isolate a mutant defective in activation. One mutant with a disruption in a sodium/hydrogen exchanger (NHE) showed both delayed exit and reduced Toxoplasma cell death after sustained ionophore exposure. Toxoplasma lacking this plasma membrane pump also had normal internal pH, but their proton efflux was no longer prevented with an NHE inhibitor.

Resting Ca²⁺ levels were higher in mutant parasites. This would make it harder to detect any exit signal that increased these Ca²⁺ levels even further, perhaps explaining why these mutants are slow to exit. The increase in resting Ca²⁺ levels may come about if a Ca²⁺ exporter (Ca²⁺ out/H⁺ in) relies on prior action of the NHE (H⁺ out/Na⁺ in). Such a hypothetical linkage may be part of regulating Toxoplasma mobility or simply an intersection between the exit system and Toxoplasma's normal ion homeostasis.

Aparna Sreenivasan

aparnas{at}nasw.org

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Related Article

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

Gustavo Arrizabalaga, Felix Ruiz, Silvia Moreno, and John C. Boothroyd
J. Cell Biol. 2004 165: 653-662. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 669K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sreenivasan, A. Search for Related Content PubMed Articles by Sreenivasan, A. Related Collections Related Article Social Bookmarking                            What's this?