Disruption of the PfPK7 gene impairs schizogony and sporogony in the human malaria parasite Plasmodium falciparum.
PfPK7 is an orphan protein kinase of Plasmodium falciparum with maximal homology to MEK3/6 and to fungal protein kinase A proteins in its C-terminal and N-terminal regions, respectively. We showed previously that recombinant PfPK7 is active on various substrates but is unable to phosphorylate the Plasmodium falciparum mitogen-activated protein kinase homologues, suggesting that it is not a MEK functional homologue. Using a reverse genetics approach to investigate the function of this enzyme in live parasites, we now show that PfPK7(-) parasite clones display phenotypes at two stages of their life cycle: first, a decrease in the rate of asexual growth in erythrocytes associated with a lower number of daughter merozoites generated per schizont, and second, a dramatic reduction in the ability to produce oocysts in the mosquito vector. A normal asexual growth rate and the ability to produce oocysts are restored if a functional copy of the PfPK7 gene is reintroduced into the PfPK7(-) parasites. Hence, PfPK7 is involved in a pathway that regulates parasite proliferation and development.
Dorin-Semblat
Dominique
D
INSERM U609, Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
Sicard
Audrey
A
Doerig
Caroline
C
Ranford-Cartwright
Lisa
L
Doerig
Christian
C
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D016778:Malaria, Falciparum / Q000201:enzymology* / Q000469:parasitology / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000502:physiology*; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology*; D013172:Spores, Fungal / Q000254:growth & development*
D015800:Protozoan Proteins; C503375:PK7 protein, Plasmodium falciparum; D020929:Mitogen-Activated Protein Kinase Kinases