Rounding precedes rupture and breakdown of vacuolar membranes minutes before malaria parasite egress from erythrocytes.

Rounding precedes rupture and breakdown of vacuolar membranes minutes before malaria parasite egress from erythrocytes.
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DOI:
10.1111/cmi.12868
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发表时间:
2018-10
影响因子:
3.4
通讯作者:
Zimmerberg J
Zimmerberg J
中科院分区:
生物学2区
文献类型:
--
作者:
Glushakova S;Beck JR;Garten M;Busse BL;Nasamu AS;Tenkova-Heuser T;Heuser J;Goldberg DE;Zimmerberg J

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由于恶性疟原虫在人类红细胞内的寄生液泡 (PV) 内复制,因此寄生虫的排出需要两个限制膜的破裂。寄生虫 Ca2+、激酶和蛋白酶有助于有效排出;它们在空间和时间上的协调尚不清楚。在这里,使用表达 PV 靶向荧光蛋白的寄生虫的活细胞显微镜和特定的出口抑制剂,将寄生虫出口的动力学与具有特定隔室标记的特定步骤联系起来。出口前几分钟,在寄生物 [Ca2+]i 的控制下,寄生液泡开始变圆。然后约 1.5 分钟后,在 PfPKG 和 SUB1 的控制下,PV 膜突然破裂并释放液泡内容物。在接下来的大约 6 分钟内,液泡膜逐渐退化,同时红细胞膜变形,一直持续到出口程序的最后一分钟,此时新形成的寄生虫动员起来,红细胞膜透化,然后破裂——这是寄生虫复制周期的戏剧性结局。
Because Plasmodium falciparum replicates inside of a parasitophorous vacuole (PV) within a human erythrocyte, parasite egress requires the rupture of two limiting-membranes. Parasite Ca2+, kinases, and proteases contribute to efficient egress; their coordination in space and time is not known. Here the kinetics of parasite egress were linked to specific steps with specific compartment markers, using live cell microscopy of parasites expressing PV-targeted fluorescent proteins, and specific egress inhibitors. Several minutes before egress, under control of parasite [Ca2+]i the parasitophorous vacuole began rounding. Then after ~1.5 minutes, under control of PfPKG and SUB1, there was abrupt rupture of the PV membrane and release of vacuolar contents. Over the next ~6 minutes there was progressive vacuolar membrane deterioration simultaneous with erythrocyte membrane distortion, lasting until the final minute of the egress program when newly-formed parasites mobilized, erythrocyte membranes permeabilized and then ruptured – a dramatic finale to the parasite cycle of replication.
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