Journal of Biochemistry Advance Access originally published online on October 9, 2006
Journal of Biochemistry 2006 140(5):747-757; doi:10.1093/jb/mvj205
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© 2006 The Japanese Biochemical Society.
ARTICLE |
PbGCß Is Essential for Plasmodium Ookinete Motility to Invade Midgut Cell and for Successful Completion of Parasite Life Cycle in Mosquitoes
1 Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Tochigi, 329-0498; and 2 Department of Tropical Medicine and Parasitology, Dokkyo University, School of Medicine, Tochigi, 321-0293
To whom correspondence should be addressed. Tel: +81-285-58-7339, Fax: +81-285-44-6489, E-mail: mhirai{at}ms.jichi.ac.jp
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 PbGCß. We demonstrated that transgenic parasites in which the PbGCß 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 PbGCß is essential for ookinete motility when passing through the midgut cells, but not for further development of the parasites.