A calcium-dependent protein kinase regulates Plasmodium ookinete access to the midgut epithelial cell
A calcium-dependent protein kinase regulates Plasmodium ookinete access to the midgut epithelial cell
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DOI：
10.1111/j.1365-2958.2005.05014.x
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发表时间：
2006-02-01
影响因子：
3.6
通讯作者：
Yuda, M
中科院分区：
文献类型：
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作者：
Ishino, T;Orito, Y;Yuda, M
疟原虫寄生虫在蚊子中肠中受精并发育成运动的受精卵，称为动合子，其侵入中肠上皮。在这里，我们表明，钙依赖性蛋白激酶，CDPK3，啮齿类疟疾寄生虫（伯氏疟原虫）的产生在动合子阶段，并在寄生虫传播到蚊子载体的关键作用。靶向破坏CDPK3基因使动合子感染蚊子中肠的能力降低了近两个数量级。电子显微镜分析表明，破坏动合子不能通过穿越覆盖细胞表面的层进入中肠上皮细胞。体外迁移试验表明，这些动合子缺乏通过人工凝胶迁移的能力，这表明这种缺陷导致它们无法进入上皮。体外迁移试验也表明，这种运动性是诱导野生型细胞内储存的钙的动员。这些结果表明，涉及钙和CDPK3的信号通路调节动合子穿透覆盖中肠上皮的层。由于人类不具有CDPK家族蛋白，因此CDPK3是阻断疟疾传播至蚊子媒介的良好靶标。
Plasmodium parasites are fertilized in the mosquito midgut and develop into motile zygotes, called ookinetes, which invade the midgut epithelium. Here we show that a calcium-dependent protein kinase, CDPK3, of the rodent malarial parasite (Plasmodium berghei) is produced in the ookinete stage and has a critical role in parasite transmission to the mosquito vector. Targeted disruption of the CDPK3 gene decreased ookinete ability to infect the mosquito midgut by nearly two orders of magnitude. Electron microscopic analyses demonstrated that the disruptant ookinetes could not access midgut epithelial cells by traversing the layer covering the cell surface. An in vitro migration assay showed that these ookinetes lack the ability to migrate through an artificial gel, suggesting that this defect caused their failure to access the epithelium. In vitro migration assays also suggested that this motility is induced in the wild type by mobilization of intracellular stored calcium. These results indicate that a signalling pathway involving calcium and CDPK3 regulates ookinete penetration of the layer covering the midgut epithelium. Because humans do not possess CDPK family proteins, CDPK3 is a good target for blocking malarial transmission to the mosquito vector.