Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite
Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite
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DOI：
10.1016/s0092-8674(04)00449-0
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发表时间：
2004-05-14
期刊：
影响因子：
64.5
通讯作者：
Brinkmann, V
中科院分区：
文献类型：
--
作者：
Billker, O;Dechamps, S;Brinkmann, V
疟疾寄生虫向蚊子的传播是由蚊子血液中寄生虫的强制性性繁殖引起的。在特定的传播阶段，配子细胞分化为雄性和雌性配子是由一种蚊子小分子黄嘌呤酸（XA）诱导的。利用表达生物发光钙传感器的伯氏疟原虫菌株，我们发现XA触发了细胞内钙的快速上升，特别是在配子细胞中，这是它们分化为配子所必需的。CDPK4是植物样钙依赖蛋白激酶家族的一员，被认为是通过调节雄性配子体的细胞周期进程将xa诱导的钙信号转化为细胞反应的分子开关。CDPK4被证明是柏氏疟原虫有性繁殖和蚊子传播的必要基因。本研究揭示了一种植物样信号通路在疟原虫细胞周期调控和生命周期进程中的意想不到的功能。
Transmission of malaria parasites to mosquitoes is initiated by the obligatory sexual reproduction of the parasite within the mosquito bloodmeal. Differentiation of specialized transmission stages, the gametocytes, into male and female gametes is induced by a small mosquito molecule, xanthurenic acid (XA). Using a Plasmodium berghei strain expressing a bioluminescent calcium sensor, we show that XA triggers a rapid rise in cytosolic calcium specifically in gametocytes that is essential for their differentiation into gametes. A member of a family of plant-like calcium dependent protein kinases, CDPK4, is identified as the molecular switch that translates the XA-induced calcium signal into a cellular response by regulating cell cycle progression in the male gametocyte. CDPK4 is shown to be essential for the sexual reproduction and mosquito transmission of P. berghei. This study reveals an unexpected function for a plant-like signaling pathway in cell cycle regulation and life cycle progression of a malaria parasite.