Cytoplasmic free Ca2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes.
Cytoplasmic free Ca2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes.
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DOI：
10.1186/1475-2875-12-41
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发表时间：
2013-01-30
期刊：
影响因子：
3
通讯作者：
Zimmerberg J
中科院分区：
文献类型：
--
作者：
Glushakova S;Lizunov V;Blank PS;Melikov K;Humphrey G;Zimmerberg J
恶性疟原虫在其无性周期结束时从红细胞中排出，随后寄生虫侵入新的宿主细胞，是人体内寄生虫传播的原因。出口途径正在成为一个协调的多步骤程序，在时间上延长了几十分钟，结束了快速寄生虫挤出红细胞。虽然Ca 2+调节恶性疟原虫在红细胞中的侵袭已经很好地建立，但Ca 2+在寄生虫排出中的作用知之甚少。本研究分析了疟疾寄生虫的多步骤出口计划期间，受感染的红细胞胞质游离Ca 2+的参与。活细胞荧光显微镜被用来成像寄生虫出口受感染的红细胞，评估药物调节Ca 2+稳态的出口方案的影响。发现胞质游离Ca 2+的稳定增加先于寄生虫出口。这种增加至少在周期的最后两个小时内不依赖于细胞外Ca 2+，但依赖于内部储存的Ca 2+释放。在周期的最后45分钟内，细胞内BAPTA螯合Ca 2+抑制寄生虫空泡肿胀和红细胞膜穿孔之前的出口，这是寄生虫出口之前的两个特征性形态学转变。寄生虫内质网（ER）Ca 2 +-ATP酶的抑制剂加速寄生虫的出口，表明ER内的Ca 2+储存足以支持出口。明显加速出口的明显可行的寄生虫实现了在成熟的cathionts使用Ca 2+离子载体A23187。离子载体治疗克服了BAPTA诱导的寄生虫出口阻滞，证实游离Ca 2+在出口启动中是必不可少的。离子载体处理未成熟的寄生虫有不良影响，诱导寄生空泡肿胀和杀死宿主细胞内的寄生虫。寄生虫出口程序需要细胞内游离Ca 2+的出口启动，液泡肿胀，宿主细胞骨架消化。寄生虫空泡肿胀，一个阶段的不受影响的出口，是依赖于细胞内Ca 2+的上升的证据表明，离子载体诱导的出口机制和一个新的目标Ca 2+在程序中解放寄生虫从宿主细胞。提出了一种依赖于细胞内游离Ca 2+增加的出口调节途径。
Egress of Plasmodium falciparum, from erythrocytes at the end of its asexual cycle and subsequent parasite invasion into new host cells, is responsible for parasite dissemination in the human body. The egress pathway is emerging as a coordinated multistep programme that extends in time for tens of minutes, ending with rapid parasite extrusion from erythrocytes. While the Ca2+ regulation of the invasion of P. falciparum in erythrocytes is well established, the role of Ca2+ in parasite egress is poorly understood. This study analysed the involvement of cytoplasmic free Ca2+ in infected erythrocytes during the multistep egress programme of malaria parasites. Live-cell fluorescence microscopy was used to image parasite egress from infected erythrocytes, assessing the effect of drugs modulating Ca2+ homeostasis on the egress programme. A steady increase in cytoplasmic free Ca2+ is found to precede parasite egress. This increase is independent of extracellular Ca2+ for at least the last two hours of the cycle, but is dependent upon Ca2+ release from internal stores. Intracellular BAPTA chelation of Ca2+ within the last 45 minutes of the cycle inhibits egress prior to parasitophorous vacuole swelling and erythrocyte membrane poration, two characteristic morphological transformations preceding parasite egress. Inhibitors of the parasite endoplasmic reticulum (ER) Ca2+-ATPase accelerate parasite egress, indicating that Ca2+ stores within the ER are sufficient in supporting egress. Markedly accelerated egress of apparently viable parasites was achieved in mature schizonts using Ca2+ ionophore A23187. Ionophore treatment overcomes the BAPTA-induced block of parasite egress, confirming that free Ca2+ is essential in egress initiation. Ionophore treatment of immature schizonts had an adverse effect inducing parasitophorous vacuole swelling and killing the parasites within the host cell. The parasite egress programme requires intracellular free Ca2+ for egress initiation, vacuole swelling, and host cell cytoskeleton digestion. The evidence that parasitophorous vacuole swelling, a stage of unaffected egress, is dependent upon a rise in intracellular Ca2+ suggests a mechanism for ionophore-inducible egress and a new target for Ca2+ in the programme liberating parasites from the host cell. A regulatory pathway for egress that depends upon increases in intracellular free Ca2+ is proposed.
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影响因子：
3
作者：
Glushakova S;Yin D;Gartner N;Zimmerberg J
通讯作者：
Zimmerberg J
影响因子：
3.4
作者：
Blackman, Michael J.
通讯作者：
Blackman, Michael J.
影响因子：
16.6
作者：
Gruering, Christof;Heiber, Arlett;Spielmann, Tobias
通讯作者：
Spielmann, Tobias
影响因子：
3
作者：
Hanssen, Eric;Knoechel, Christian;Tilley, Leann
通讯作者：
Tilley, Leann
影响因子：
64.8
作者：
Eckstein-Ludwig, U;Webb, RJ;Krishna, S
通讯作者：
Krishna, S