title: An essential role for the Plasmodium Nek-2 Nima-related protein kinase in the sexual development of malaria parasites.
abstract: The molecular control of cell division and development in malaria parasites is far from understood. We previously showed that a Plasmodium gametocyte-specific NIMA-related protein kinase, nek-4, is required for completion of meiosis in the ookinete, the motile form that develops from the zygote in the mosquito vector. Here, we show that another NIMA-related kinase, Pfnek-2, is also predominantly expressed in gametocytes, and that Pfnek-2 is an active enzyme displaying an in vitro substrate preference distinct from that of Pfnek-4. A functional nek-2 gene is required for transmission of both Plasmodium falciparum and the rodent malaria parasite Plasmodium berghei to the mosquito vector, which is explained by the observation that disruption of the nek-2 gene in P. berghei causes dysregulation of DNA replication during meiosis and blocks ookinete development. This has implications (i) in our understanding of sexual development of malaria parasites and (ii) in the context of control strategies aimed at interfering with malaria transmission.
authors.affiliation: INSERM U609-Wellcome Centre for Molecular Parasitology, Biomedical Research Centre, Faculty of Biomedical and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, Scotland.
authors.forename: Luc
authors.initials: L
authors.lastname: Reininger
authors.forename: Rita
authors.initials: R
authors.lastname: Tewari
authors.forename: Clare
authors.initials: C
authors.lastname: Fennell
authors.forename: Zoe
authors.initials: Z
authors.lastname: Holland
authors.forename: Dean
authors.initials: D
authors.lastname: Goldring
authors.forename: Lisa
authors.initials: L
authors.lastname: Ranford-Cartwright
authors.forename: Oliver
authors.initials: O
authors.lastname: Billker
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins / Q000378:metabolism*; D009033:Culicidae / Q000469:parasitology; D004261:DNA Replication; D004912:Erythrocytes / Q000469:parasitology; D020869:Gene Expression Profiling; D018390:Gene Targeting; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008018:Life Cycle Stages; D016778:Malaria, Falciparum / Q000201:enzymology* / Q000469:parasitology / Q000635:transmission; D008540:Meiosis; D008969:Molecular Sequence Data; D000072380:NIMA-Related Kinase 1; D010271:Parasites / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D010641:Phenotype; D010962:Plasmodium berghei / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D046468:Sexual Development
chemical_list: D018797:Cell Cycle Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C000606914:NEK1 protein, human; D000072380:NIMA-Related Kinase 1; D017346:Protein Serine-Threonine Kinases