Essential role of membrane-attack protein in malarial transmission to mosquito host
Essential role of membrane-attack protein in malarial transmission to mosquito host
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DOI：
10.1073/pnas.0406187101
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发表时间：
2004-11-16
影响因子：
11.1
通讯作者：
Yuda, M
中科院分区：
文献类型：
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作者：
Kadota, K;Ishino, T;Yuda, M
蚊子摄入受感染的血液后，疟疾寄生虫在蚊子中肠中受精并发育成能动的动动子。这些动动物通过破坏细胞膜侵入上皮细胞，并通过细胞质向基底层迁移，并在基底层上发育成卵囊。在这里，我们报道了一种具有膜攻击复合物和穿孔素（MACPF）相关结构域的微线体蛋白，我们将其命名为膜攻击动动物蛋白（MAOP），它是在动动物阶段产生的，并且在动动物入侵中肠中发挥重要作用。带有 MAOP 基因的动植物被破坏，完全失去了对中肠的感染性。在摄入被破坏的寄生虫感染的血液后，中肠上皮保持完整，这与野生型动动物侵入的受损中肠上皮形成鲜明对比。电子显微镜分析表明，破坏性动动子迁移到肠上皮并在顶端附着在细胞表面，但无法通过破坏细胞膜进入细胞质。这些结果表明，MAOP 分子作用于宿主细胞样哺乳动物 MACPF 家族蛋白的质膜，这些蛋白在靶细胞膜上形成孔。另一种先前鉴定的 MACPF 相关分子是在肝脏感染子孢子中产生的，在穿过肝窦细胞边界时发挥着至关重要的作用。因此，目前的发现表明，涉及 MACPF 相关蛋白的保守膜破裂机制被用于疟疾寄生虫的不同宿主侵入阶段，在突破宿主器官的生物屏障方面发挥着关键作用。
After ingestion of infected blood by a mosquito, malarial parasites are fertilized in the mosquito midgut and develop into motile ookinetes. These ookinetes invade epithelial cells by rupturing the cell membrane and migrate through the cytoplasm toward the basal lamina, on which they develop to oocysts. Here we report that a microneme protein with a membrane-attack complex and perforin (MACPF)-related domain, which we name membrane-attack ookinete protein (MAOP), is produced in the ookinete stage and plays an essential role in midgut invasion by the ookinete. Ookinetes with the MAOP gene disrupted completely lost infectivity to the midgut. After ingestion of blood infected with the disrupted parasite, the midgut epithelium remained intact, making a clear contrast with the damaged midgut epithelium invaded by wild-type ookinetes. Electron microscopic analysis showed that the disruptant ookinetes migrate to the gut epithelium and attach to the cell surface at the apical tip, but are unable to enter the cytoplasm by rupturing the cell membrane. These results indicate that the MAOP molecule acts on the plasma membrane of the host-cell-like mammalian MACPF family proteins that create pores in the membrane of target cells. Another previously identified MACPF-related molecule is produced in the liver-infective sporozoite and has a crucial role in traversing the liver sinusoidal cell boundary. The present finding, thus, suggests that conserved mechanisms for membrane rupture involving MACPF-related proteins are used in different host invasive stages of the malarial parasite, playing a key role in breaching biological barriers of host organs.