International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India.
School of Life Sciences, University of Nottingham, Nottingham, NG72UH, UK.
Sci Rep. 2017 Nov 14;7(1):15577. doi: 10.1038/s41598-017-15781-z.
Plasmodium parasites, the causative agents of malaria, possess a distinctive membranous structure of flattened alveolar vesicles supported by a proteinaceous network, and referred to as the inner membrane complex (IMC). The IMC has a role in actomyosin-mediated motility and host cell invasion. Here, we examine the location, protein interactome and function of PhIL1, an IMC-associated protein on the motile and invasive stages of both human and rodent parasites. We show that PhIL1 is located in the IMC in all three invasive (merozoite, ookinete-, and sporozoite) stages of development, as well as in the male gametocyte and locates both at the apical and basal ends of ookinete and sporozoite stages. Proteins interacting with PhIL1 were identified, showing that PhIL1 was bound to only some proteins present in the glideosome motor complex (GAP50, GAPM1-3) of both P. falciparum and P. berghei. Analysis of PhIL1 function using gene targeting approaches indicated that the protein is required for both asexual and sexual stages of development. In conclusion, we show that PhIL1 is required for development of all zoite stages of Plasmodium and it is part of a novel protein complex with an overall composition overlapping with but different to that of the glideosome.
疟原虫寄生虫是疟疾的病原体,它们具有独特的扁囊泡膜结构,由蛋白质网络支撑,被称为内膜复合物(IMC)。IMC 在肌动球蛋白介导的运动和宿主细胞入侵中起作用。在这里,我们研究了 PhIL1 的位置、蛋白质相互作用组和功能,PhIL1 是一种与 IMC 相关的蛋白质,存在于人类和啮齿动物寄生虫的运动和侵袭阶段。我们表明,PhIL1 存在于所有三个侵袭性(裂殖子、动合子和孢子)发育阶段的 IMC 中,以及雄性配子体中,并且位于动合子和孢子阶段的顶端和基部。鉴定了与 PhIL1 相互作用的蛋白质,表明 PhIL1 仅与 Pfalciparum 和 Pberghei 中的滑行体运动复合物(GAP50、GAPM1-3)中的一些蛋白质结合。使用基因靶向方法分析 PhIL1 的功能表明,该蛋白对于无性和有性发育阶段都是必需的。总之,我们表明 PhIL1 是疟原虫所有裂殖体阶段发育所必需的,它是一个新的蛋白质复合物的一部分,其总体组成与滑行体重叠但不同。