Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite

被引:395
作者
Billker, O [1 ]
Dechamps, S
Tewari, R
Wenig, G
Franke-Fayard, B
Brinkmann, V
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Sci Biol, London SW7 2AZ, England
[2] Leiden Univ, Med Ctr, Parasitol Lab, NL-2300 RC Leiden, Netherlands
[3] Max Planck Inst Infekt Biol, D-10117 Berlin, Germany
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0092-8674(04)00449-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
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.
引用
收藏
页码:503 / 514
页数:12
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