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

被引:55
作者
Arrizabalaga, G
Ruiz, F
Moreno, S
Boothroyd, JC
机构
[1] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA
[2] Univ Illinois, Dept Pathobiol, Mol Parasitol Lab, Urbana, IL 61802 USA
[3] Univ Illinois, Dept Pathobiol, Ctr Zoonoses Res, Urbana, IL 61802 USA
关键词
Toxoplasma; ionophore; egress; calcium; NHE;
D O I
10.1083/jcb.200309097
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:653 / 662
页数:10
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