A calcium‐dependent protein kinase regulates Plasmodium ookinete access to the midgut epithelial cell

Summary 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 stag...

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Bibliographic Details
Published in:Molecular microbiology 2006-02, Vol.59 (4), p.1175-1184
Main Authors: Ishino, Tomoko, Orito, Yuki, Chinzei, Yasuo, Yuda, Masao
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Calcium
Cell Movement - genetics
Collagen - metabolism
Culicidae - cytology
Culicidae - parasitology
Drug Combinations
Epithelial Cells - parasitology
Female
Fundamental and applied biological sciences. Psychology
Genes, Protozoan
Laminin - metabolism
Malaria
Malaria - parasitology
Mice
Mice, Inbred BALB C
Microbiology
Mosquitoes
Oocysts - enzymology
Oocysts - pathogenicity
Parasites
Plasmodium berghei
Plasmodium berghei - enzymology
Plasmodium berghei - pathogenicity
Protein Kinases - genetics
Protein Kinases - metabolism
Proteins
Proteoglycans - metabolism
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Rats
Rats, Wistar
Sequence Deletion
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Summary:Summary 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.
ISSN:0950-382X
1365-2958
DOI:10.1111/j.1365-2958.2005.05014.x