An essential role for the Plasmodium Nek-2 Nima-related protein kinase in the sexual development of malaria parasites.
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.
Reininger
Luc
L
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.
Tewari
Rita
R
Fennell
Clare
C
Holland
Zoe
Z
Goldring
Dean
D
Ranford-Cartwright
Lisa
L
Billker
Oliver
O
Doerig
Christian
C
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
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