title: Functional characterization of both MAP kinases of the human malaria parasite Plasmodium falciparum by reverse genetics.
abstract: The kinome of the human malaria parasite Plasmodium falciparum includes two genes encoding mitogen-activated protein kinase (MAPK) homologues, pfmap-1 and pfmap-2, but no clear orthologue of the MAPK kinase (MAPKK) family, raising the question of the mode of activation and function of the plasmodial MAPKs. Functional studies in the rodent malaria model Plasmodium berghei recently showed the map-2 gene to be dispensable for asexual growth and gametocytogenesis, but essential for male gametogenesis in the mosquito vector. Here, we demonstrate by using a reverse genetics approach that the map-2 gene is essential for completion of the asexual cycle of P. falciparum, an unexpected result in view of the non-essentiality of the orthologous gene for P. berghei erythrocytic schizogony. This validates Pfmap-2 as a potential target for chemotherapeutic intervention. In contrast, the other P. falciparum MAPK, Pfmap-1, is required neither for in vitro schizogony and gametocytogenesis in erythrocytes, nor for gametogenesis and sporogony in the mosquito vector. However, Pfmap-2 protein levels are elevated in pfmap-1(-) parasites, suggesting that Pfmap-1 fulfils an important function in asexual parasites that necessitates compensatory adaptation in parasites lacking this enzyme.
authors.affiliation: INSERM U609, Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: Dominique
authors.initials: D
authors.lastname: Dorin-Semblat
authors.forename: Neils
authors.initials: N
authors.lastname: Quashie
authors.forename: Jean
authors.initials: J
authors.lastname: Halbert
authors.forename: Audrey
authors.initials: A
authors.lastname: Sicard
authors.forename: Caroline
authors.initials: C
authors.lastname: Doerig
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Peat
authors.forename: Lisa
authors.initials: L
authors.lastname: Ranford-Cartwright
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D016778:Malaria, Falciparum; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000502:physiology; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D015800:Protozoan Proteins; D020928:Mitogen-Activated Protein Kinases