title: A calcium-dependent protein kinase regulates Plasmodium ookinete access to the midgut epithelial cell.
abstract: 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.
authors.affiliation: Department of Medical Zoology, Mie University School of Medicine, Edobashi, Tsu, Mie 514-0001, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishino
authors.forename: Yuki
authors.initials: Y
authors.lastname: Orito
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Chinzei
authors.forename: Masao
authors.initials: M
authors.lastname: Yuda
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D009033:Culicidae / Q000166:cytology / Q000469:parasitology*; D004338:Drug Combinations; D004847:Epithelial Cells / Q000469:parasitology; D005260:Female; D017125:Genes, Protozoan; D007797:Laminin / Q000378:metabolism; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D033661:Oocysts / Q000201:enzymology / Q000472:pathogenicity*; D010962:Plasmodium berghei / Q000201:enzymology / Q000472:pathogenicity*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017384:Sequence Deletion; D017871:Calcium-Calmodulin-Dependent Protein Kinases
chemical_list: D003094:Collagen; D004338:Drug Combinations; D007797:Laminin; D011494:Protein Kinases; D011509:Proteoglycans; D015800:Protozoan Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C059485:matrigel