A processing product of thePlasmodium falciparumreticulocyte binding proteinRH1shows a close association withAMA1during junction formation
A processing product of thePlasmodium falciparumreticulocyte binding proteinRH1shows a close association withAMA1during junction formation
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DOI：
10.1111/cmi.13232
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发表时间：
2020-06-17
影响因子：
3.4
通讯作者：
Preiser, Peter R.
中科院分区：
文献类型：
--
作者：
Gunalan, Karthigayan;Gao, Xiaohong;Preiser, Peter R.
恶性疟原虫（Plasmodium falciparum负责最致命形式的疟疾）通过多种配体受体相互作用侵入人红细胞。就会。恶性粒细胞结合蛋白同源物（PfRHs）在分裂子的顶端表达，并与不同的红细胞表面受体形成相互作用，这对侵袭很重要。在这里，我们使用一系列针对PfRH1不同区域的单克隆抗体（mab）研究了PfRH加工在分裂子侵入过程中的作用。我们发现PfRH1在分裂子成熟和入侵过程中得到不同的加工，并提供了不同的PfRH1加工产物在入侵过程中具有不同的功能的证据。通过原位接近结扎和FRET检测，我们发现PfRH1产物的一个亚群在移动连接中与微分子蛋白顶端膜抗原1 （Apical Membrane Antigen 1, AMA1）密切相关，这表明PfRH1在促进连接形成和主动侵袭中起关键作用。我们的数据提供了证据，证明PfRH蛋白的时间依赖性加工是寄生虫能够调节这些大过程的不同功能活动的机制。现在鉴定出与AMA1在连接处的特定密切关联也可能提供新的途径来靶向这些相互作用以防止分裂子侵入。
Plasmodium falciparumresponsible for the most virulent form of malaria invades human erythrocytes through multiple ligand-receptor interactions. TheP. falciparumreticulocyte binding protein homologues (PfRHs) are expressed at the apical end of merozoites and form interactions with distinct erythrocyte surface receptors that are important for invasion. Here using a range of monoclonal antibodies (mAbs) against different regions of PfRH1 we have investigated the role of PfRH processing during merozoite invasion. We show that PfRH1 gets differentially processed during merozoite maturation and invasion and provide evidence that the different PfRH1 processing products have distinct functions during invasion. Using in-situ Proximity Ligation and FRET assays that allow probing of interactions at the nanometre level we show that a subset of PfRH1 products form close association with micronemal proteins Apical Membrane Antigen 1 (AMA1) in the moving junction suggesting a critical role in facilitating junction formation and active invasion. Our data provides evidence that time dependent processing of PfRH proteins is a mechanism by which the parasite is able to regulate distinct functional activities of these large processes. The identification of a specific close association with AMA1 in the junction now may also provide new avenues to target these interactions to prevent merozoite invasion.