Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum.
Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum.
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DOI：
10.1038/nature10606
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发表时间：
2011-11-09
期刊：
影响因子：
64.8
通讯作者：
Wright, Gavin J.
中科院分区：
文献类型：
--
作者：
Crosnier, Cecile;Bustamante, Leyla Y.;Bartholdson, S. Josefin;Bei, Amy K.;Theron, Michel;Uchikawa, Makoto;Mboup, Souleymane;Ndir, Omar;Kwiatkowski, Dominic P.;Duraisingh, Manoj T.;Rayner, Julian C.;Wright, Gavin J.
恶性疟原虫对红细胞的侵袭是疟疾发病机制的核心。入侵需要红细胞受体和裂殖子上的配体之间发生一系列细胞外识别事件，裂殖子是寄生虫的入侵形式。已知的为数不多的受体-配体相互作用在所有寄生虫株中都不是必需的，这表明寄生虫能够进入多条多余的入侵途径。在这里，我们表明，我们已经在所有测试的恶性疟原虫株中发现了一对对红细胞入侵至关重要的受体-配体对。通过系统地筛选红细胞蛋白质文库，我们发现OK血型抗原basigin是PfRh5的受体，PfRh5是一种寄生虫配体，对血液阶段的生长至关重要。可溶性basigin或basigin基因敲除可有效抑制红细胞侵袭，低浓度的抗basigin抗体可完全阻断红细胞侵袭；重要的是，在所有实验室适应和现场测试的菌株中都观察到了这些影响。此外，表达Basigin变体的OK(a−)红细胞与PfRh5的结合亲和力较弱，表现出较低的侵袭效率。我们发现恶性疟原虫对红细胞的侵袭依赖于单个细胞外受体-配体对，这一发现为新的抗疟疾治疗提供了一个焦点。
Erythrocyte invasion by Plasmodium falciparum is central to the pathogenesis of malaria. Invasion requires a series of extracellular recognition events between erythrocyte receptors and ligands on the merozoite, the invasive form of the parasite. None of the few known receptor-ligand interactions involved are required in all parasite strains suggesting that the parasite is able to access multiple redundant invasion pathways. Here, we show that we have identified a receptor-ligand pair that is essential for erythrocyte invasion in all tested P. falciparum strains. By systematically screening a library of erythrocyte proteins, we have found that the Ok blood group antigen, BASIGIN, is a receptor for PfRh5, a parasite ligand that is essential for blood stage growth. Erythrocyte invasion was potently inhibited by soluble BASIGIN or by BASIGIN knockdown, and invasion could be completely blocked using low concentrations of anti-BASIGIN antibodies; importantly, these effects were observed across all laboratory-adapted and field strains tested. Furthermore, Ok(a−) erythrocytes, which express a BASIGIN variant that has a weaker binding affinity for PfRh5, exhibited reduced invasion efficiencies. Our discovery of a cross-strain dependency on a single extracellular receptor-ligand pair for erythrocyte invasion by P. falciparum provides a focus for novel anti-malarial therapies.
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