Organization and function of an actin cytoskeleton in Plasmodium falciparum gametocytes

Organization and function of an actin cytoskeleton in Plasmodium falciparum gametocytes
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DOI:
10.1111/cmi.12359
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发表时间:
2015-02-01
影响因子:
3.4
通讯作者:
Tilley, Leann
Tilley, Leann
中科院分区:
生物学2区
文献类型:
--
作者:
Hliscs, Marion;Millet, Coralie;Tilley, Leann

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恶性疟原虫是人类疟疾寄生虫中最致命的一种,为了准备传播给其蚊子媒介,它采用了一种不寻常的细长形状。在这里,我们描述了一个以前未被识别的基于动作蛋白的细胞骨架,它是在成熟的恶性疟原虫配子体细胞中组装的。差异提取揭示了在发育的所有阶段都存在高度稳定的f -肌动蛋白群体。超分辨率显微镜显示一个f -肌动蛋白细胞骨架,它集中在细长配子体的末端,但沿着微管细胞骨架向内延伸。Formin-1也集中在配子体末端,这表明它在肌动蛋白稳定中起作用。免疫电镜证实肌动蛋白细胞骨架位于内膜复合体下方,而不是在肺泡下。在V期配子体中,肌动蛋白和微管细胞骨架以协调的方式重组。肌动蛋白解聚剂,细胞松弛素D,从配子体末端消耗肌动蛋白,而肌动蛋白稳定化合物,茉莉素内酯,诱导形成大束,防止肌动蛋白细胞骨架的后期解体。这些化合物的长期治疗与正常线粒体组织的破坏和配子细胞活力的降低有关。
In preparation for transmission to its mosquito vector, Plasmodium falciparum, the most virulent of the human malaria parasites, adopts an unusual elongated shape. Here we describe a previously unrecognized actin-based cytoskeleton that is assembled in maturing P. falciparum gametocytes. Differential extraction reveals the presence of a highly stabilized population of F-actin at all stages of development. Super-resolution microscopy reveals an F-actin cytoskeleton that is concentrated at the ends of the elongating gametocyte but extends inward along the microtubule cytoskeleton. Formin-1 is also concentrated at the gametocyte ends suggesting a role in actin stabilization. Immunoelectron microscopy confirms that the actin cytoskeleton is located under the inner membrane complex rather than in the sub-alveolar space. In stage V gametocytes, the actin and microtubule cytoskeletons are reorganized in a coordinated fashion. The actin-depolymerizing agent, cytochalasin D, depletes actin from the end of the gametocytes, whereas the actin-stabilizing compound, jasplakinolide, induces formation of large bundles and prevents late-stage disassembly of the actin cytoskeleton. Long-term treatment with these compounds is associated with disruption of the normal mitochondrial organization and decreased gametocyte viability.