Calcium signaling in a low calcium environment: how the intracellular malaria parasite solves the problem.

Calcium signaling in a low calcium environment: how the intracellular malaria parasite solves the problem.
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低钙环境中的钙信号传导:细胞内疟疾寄生虫如何解决该问题。

DOI:
10.1083/jcb.200212130
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发表时间:
2003-04-14
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Garcia CR
Garcia CR
中科院分区:
其他
文献类型:
--
作者:
Gazarini ML;Thomas AP;Pozzan T;Garcia CR

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疟疾寄生虫,疟原虫,在红细胞内度过了它们无性生命周期的大部分时间,在那里它们增殖和成熟。红细胞质具有非常低的[Ca2+](<100 nM),这与大多数真核细胞遇到的细胞外环境非常不同。细胞外Ca2+的缺乏通常与正常细胞功能和存活不相容。在目前的工作中,我们已经测试的可能性,疟原虫克服红细胞内环境的限制,通过维持高[Ca 2 +]内的寄生虫空泡(PV),入侵期间形成的隔室,其中寄生虫生长和分裂。因此,允许疟原虫在Ca2+指示剂染料存在下侵入红细胞。这允许在PV内选择性加载Ca2+探针。发现该隔室中的[Ca2+]<40 μM,即,高到足以与疟原虫胞内Ca2+储存的正常负荷相容,这是使用基于Ca2+的信号传导机制的先决条件。我们还表明,细胞外[Ca2+]的减少导致PV内[Ca2+]的缓慢耗尽。PV中[Ca2+]短暂下降2 h会影响红细胞内寄生虫的成熟过程,48 h后寄生虫(重新侵入红细胞的形式)的百分比大幅降低。
Malaria parasites, Plasmodia, spend most of their asexual life cycle within red blood cells, where they proliferate and mature. The erythrocyte cytoplasm has very low [Ca2+] (<100 nM), which is very different from the extracellular environment encountered by most eukaryotic cells. The absence of extracellular Ca2+ is usually incompatible with normal cell functions and survival. In the present work, we have tested the possibility that Plasmodia overcome the limitation posed by the erythrocyte intracellular environment through the maintenance of a high [Ca2+] within the parasitophorous vacuole (PV), the compartment formed during invasion and within which the parasites grow and divide. Thus, Plasmodia were allowed to invade erythrocytes in the presence of Ca2+ indicator dyes. This allowed selective loading of the Ca2+ probes within the PV. The [Ca2+] within this compartment was found to be ∼40 μM, i.e., high enough to be compatible with a normal loading of the Plasmodia intracellular Ca2+ stores, a prerequisite for the use of a Ca2+-based signaling mechanism. We also show that reduction of extracellular [Ca2+] results in a slow depletion of the [Ca2+] within the PV. A transient drop of [Ca2+] in the PV for a period as short as 2 h affects the maturation process of the parasites within the erythrocytes, with a major reduction 48 h later in the percentage of schizonts, the form that re-invades the red blood cells.
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