PbGCβ is essential for Plasmodium Ookinete motility to invade midgut cell and for successful completion of parasite life cycle in mosquitoes

被引:48
作者
Hirai, Makoto [1 ]
Arai, Meiji
Kawai, Satoru
Matsuoka, Hiroyuki
机构
[1] Jichi Med Univ, Dept Infect & Immun, Div Med Zool, Minami Kawachi, Tochigi 3290498, Japan
[2] Dokkyo Univ, Sch Med, Dept Trop Med & Parasitol, Mibu, Tochigi 3210293, Japan
关键词
cell motility; gene targeting; invasion; parasitology; Plasmodium;
D O I
10.1093/jb/mvj205
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
When malaria parasites enter to mosquitoes, they fertilize and differentiate to zygotes and ookinetes. The motile ookinetes cross the midgut cells and arrive to the basement membranes where they differentiate into oocysts. The midgut epithelium is thus a barrier for ookinetes to complete their life cycle in the mosquitoes. The ookinetes develop gliding motility to invade midgut cells successfully, but the molecular mechanisms behind are poorly understood. Here, we identified a single molecule with guanylate cyclase domain and N-terminal P-type ATPase like domain in the rodent malaria parasite Plasmodium berghei and named it PbGC beta. We demonstrated that transgenic parasites in which the PbGC beta gene was disrupted formed normal ookinetes but failed to produce oocyst. Confocal microscopic analysis showed that the disruptant ookinetes remained on the surface of the microvilli. The disruptant ookinetes showed severe defect in motility, resulting in failure of parasite invasion of the midgut epithelium. When the disruptant ookinetes were cultured in vitro, they transformed into oocysts and sporozoites. These results demonstrate that PbGC beta is essential for ookinete motility when passing through the midgut cells, but not for further development of the parasites.
引用
收藏
页码:747 / 757
页数:11
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