Plasmodium falciparum aldolase and the C-terminal cytoplasmic domain of certain apical organellar proteins promote actin polymerization.

Plasmodium falciparum aldolase and the C-terminal cytoplasmic domain of certain apical organellar proteins promote actin polymerization.
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DOI:
10.1016/j.molbiopara.2014.09.006
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发表时间:
2014-10
影响因子:
1.5
通讯作者:
Holder AA
Holder AA
中科院分区:
医学4区
文献类型:
--
作者:
Diaz SA;Martin SR;Grainger M;Howell SA;Green JL;Holder AA

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目前的Apicomplexan运动和宿主细胞侵袭的模型是,这两个过程都是由位于质膜下的肌动蛋白马达驱动的,力通过醛缩酶和某些1型膜蛋白的细胞质尾区(CTD)耦合传递到细胞外部。在恶性疟原虫(PF)中,醛缩酶被认为与血栓反应蛋白相关匿名蛋白(TRAP)家族成员的CTD结合,该家族是一种微核蛋白,在裂殖子中以MTRAP为代表。其他1型膜蛋白,包括红细胞结合抗原(EBA)和网织红细胞结合蛋白同源(RH)家族的成员,也是顶端细胞器蛋白,也参与了与宿主细胞结合的红细胞入侵。然而,最近对弓形虫的研究质疑了醛缩酶在这些过程中的重要性。利用生物分子层干涉计量学,我们发现PF醛缩酶与兔肌动蛋白和PF肌动蛋白都有很高的亲和力,与丝状(F-)肌动蛋白和球状(G-)肌动蛋白的亲和力相似。通过共沉淀实验证实了PF醛缩酶与裂殖子肌动蛋白之间的相互作用。醛缩酶结合可促进兔肌动蛋白聚合,说明这种相互作用比单独结合更为复杂。部分(但不是全部)1型膜蛋白的CTD在没有醛缩酶的情况下也促进了肌动蛋白的聚合;MTRAP和RH1 CTD促进了肌动蛋白的聚合,而EBA175 CTD则没有。由膜蛋白CTDS介导的肌动蛋白直接聚合可能有助于肌动蛋白的募集、微丝的形成和运动的稳定性,以及肌动蛋白介导的运动,而不依赖于醛缩酶。
The current model of Apicomplexan motility and host cell invasion is that both processes are driven by an actomyosin motor located beneath the plasma membrane, with the force transduced to the outside of the cell via coupling through aldolase and the cytoplasmic tail domains (CTDs) of certain type 1 membrane proteins. In Plasmodium falciparum (Pf), aldolase is thought to bind to the CTD of members of the thrombospondin-related anonymous protein (TRAP) family, which are micronemal proteins and represented by MTRAP in merozoites. Other type 1 membrane proteins including members of the erythrocyte binding antigen (EBA) and reticulocyte binding protein homologue (RH) protein families, which are also apical organellar proteins, have also been implicated in host cell binding in erythrocyte invasion. However, recent studies with Toxoplasma gondii have questioned the importance of aldolase in these processes. Using biolayer interferometry we show that Pf aldolase binds with high affinity to both rabbit and Pf actin, with a similar affinity for filamentous (F-) actin and globular (G-) actin. The interaction between Pf aldolase and merozoite actin was confirmed by co-sedimentation assays. Aldolase binding was shown to promote rabbit actin polymerization indicating that the interaction is more complicated than binding alone. The CTDs of some but not all type 1 membrane proteins also promoted actin polymerization in the absence of aldolase; MTRAP and RH1 CTDs promoted actin polymerization but EBA175 CTD did not. Direct actin polymerization mediated by membrane protein CTDs may contribute to actin recruitment, filament formation and stability during motor assembly, and actin-mediated movement, independent of aldolase.
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