Biogenesis of the crystalloid organelle in Plasmodium involves microtubule-dependent vesicle transport and assembly.

Biogenesis of the crystalloid organelle in Plasmodium involves microtubule-dependent vesicle transport and assembly.
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DOI:
10.1016/j.ijpara.2015.03.002
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发表时间:
2015-07
影响因子:
4
通讯作者:
Dessens, Johannes T.
Dessens, Johannes T.
中科院分区:
医学2区
文献类型:
--
作者:
Saeed, Sadia;Tremp, Annie Z.;Dessens, Johannes T.

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伯氏疟原虫的晶体形成发生在动细胞发育的早期阶段。从LAP3中删除LCCL结构域会导致晶体形成延迟。敲除LAP3可以阻止晶体的形成。晶体的生物发生涉及到主动的囊泡运输和组装。晶体的组装依赖于微管。疟疾寄生虫具有独特的亚细胞结构和细胞器。其中之一是晶体,这是一种在寄生虫在媒介蚊子体内发育过程中形成的多囊细胞器。这些细胞器的形成和功能仍然知之甚少。LCCL-凝集素粘附样蛋白(LAPS)是一个由六个保守的模块化蛋白组成的家族,它们在子孢子传播中起着重要作用,定位于晶体。在这项研究中,我们分析了表达GFP标记的LAP3的伯氏疟原虫转基因寄生虫的晶体形成。我们发现,LAP3中LCCL结构域的缺失会延缓晶体的发育,而LAP3的敲除则会阻止细胞器的形成。我们的数据显示,晶体的形成过程包括内质网衍生的小泡通过微管依赖的运输主动重新定位到共同的集合点。抑制微管依赖的货物运输扰乱了这一过程,并在野生型寄生虫中复制了LCCL结构域缺失突变表型。这些发现提供了对晶体生物发生的第一次清晰的洞察,展示了LAP家族在这一过程中的基本作用,并确定晶体及其形成是疟疾传播控制的潜在目标。
Crystalloid formation in Plasmodium berghei occurs during the early phase of ookinete development. Deletion of the LCCL domain from LAP3 causes delayed crystalloid formation. Knockout of LAP3 prevents crystalloid formation. Crystalloid biogenesis involves active vesicle transport and assembly. Crystalloid assembly is microtubule-dependent. Malaria parasites possess unique subcellular structures and organelles. One of these is the crystalloid, a multivesicular organelle that forms during the parasite’s development in vector mosquitoes. The formation and function of these organelles remain poorly understood. A family of six conserved and modular proteins named LCCL-lectin adhesive-like proteins (LAPs), which have essential roles in sporozoite transmission, localise to the crystalloids. In this study we analyse crystalloid formation using transgenic Plasmodium berghei parasites expressing GFP-tagged LAP3. We show that deletion of the LCCL domain from LAP3 causes retarded crystalloid development, while knockout of LAP3 prevents formation of the organelle. Our data reveal that the process of crystalloid formation involves active relocation of endoplasmic reticulum-derived vesicles to common assembly points via microtubule-dependent transport. Inhibition of microtubule-dependent cargo transport disrupts this process and replicates the LCCL domain deletion mutant phenotype in wildtype parasites. These findings provide the first clear insight into crystalloid biogenesis, demonstrating a fundamental role for the LAP family in this process, and identifying the crystalloid and its formation as potential targets for malaria transmission control.
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