Ionophore-resistant mutant of Toxoplasma gondii reveals involvement of a sodium/hydrogen exchanger in calcium regulation.
Ionophore-resistant mutant of Toxoplasma gondii reveals involvement of a sodium/hydrogen exchanger in calcium regulation.
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DOI：
10.1083/jcb.200309097
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发表时间：
2004-06-07
期刊：
影响因子：
--
通讯作者：
Boothroyd JC
中科院分区：
文献类型：
--
作者：
Arrizabalaga G;Ruiz F;Moreno S;Boothroyd JC
钙是真核细胞内许多过程的重要介质。例如，在专性细胞内寄生虫刚地弓形虫中，[Ca 2 +]的升高与显著的形态变化和从宿主细胞的快速排出有关。为了了解这种戏剧性的影响背后的机制，我们分离出一个突变体，改变其对Ca 2+离子载体A23187的反应，并发现受影响的基因编码位于寄生虫质膜上的Na+/H+交换器（NHEs）的同源物。我们发现，在TgNHE 1的情况下，弓形虫是耐离子载体诱导的出口和细胞外死亡和阿米洛利诱导的质子外排抑制。此外，突变体具有增加的细胞内Ca 2+水平，这解释了其对A23187的敏感性降低。这些结果提供了直接的遗传证据，NHE 1在Ca 2+稳态中的作用，以及对这种无处不在的病原体如何感知和响应其环境变化的重要见解。
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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影响因子：
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