Apical membrane antigen 1 plays a central role in erythrocyte invasion by Plasmodium species
Apical membrane antigen 1 plays a central role in erythrocyte invasion by Plasmodium species
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DOI：
10.1046/j.1365-2958.2000.02175.x
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发表时间：
2000-11-01
影响因子：
3.6
通讯作者：
Cowman, AF
中科院分区：
文献类型：
--
作者：
Triglia, T;Healer, J;Cowman, AF
顶膜抗原 1 (AMA1) 是一种无性血液阶段蛋白，以疟原虫属的侵入性裂殖子形式表达，疟原虫是疟疾的病原体。我们用来自 Chabaudi 疟原虫 (PcAMA1) 的不同 AMA1 转基因补充了恶性疟原虫 AMA1 (PfAMA1) 的功能。尽管我们证明 PfAMA1 基因可以通过同源重组来靶向，但使用“敲除”质粒不可能破坏 PfAMA1 基因。这些实验表明 PfAMA1 对于血液阶段的生长至关重要，甚至可能是必需的。重要的是，我们发现恶性疟原虫中的 PcAMA1 表达为人红细胞中内源性 PfAMA1 的至少 35% 的功能提供了跨物种互补。此外。该转基因在恶性疟原虫中的表达导致小鼠红细胞更有效地入侵。这些结果表明 AMA1 在红细胞 (RBC) 跨不同疟原虫物种的侵袭中发挥着重要作用。
Apical membrane antigen 1 (AMA1) is an asexual blood-stage protein expressed in the invasive merozoite form of Plasmodia species, which are the causative agent of malaria. We have complemented the function of Plasmodium falciparum AMA1 (PfAMA1) with a divergent AMA1 transgene from Plasmodium chabaudi (PcAMA1), It was not possible to disrupt the PfAMA1 gene using 'knock-out' plasmids, although we demonstrate that the PfAMA1 gene can be targeted by homologous recombination. These experiments suggest that PfAMA1 is critical, perhaps essential, for blood-stage growth. Importantly, we showed that PcAMA1 expression in P. falciparum provides trans-species complementation to at least 35% of the function of endogenous PfAMA1 in human red cells. Furthermore. expression of this transgene in P. falciparum leads to more efficient invasion of murine erythrocytes. These results indicate an important role for AMA1 in the invasion of red blood cells (RBCs) across divergent Plasmodium species.