期刊
JOURNAL OF CELL BIOLOGY
卷 165, 期 5, 页码 653-662出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200309097
关键词
Toxoplasma; ionophore; egress; calcium; NHE
类别
资金
- NIAID NIH HHS [R01 AI043614, R01 AI045051, T32 AI007328, AI45051, AI43614, AI07328-12] Funding Source: Medline
- NIGMS NIH HHS [F32 GM020872, GM20872-02] Funding Source: Medline
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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