Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 284, Issue 31, Pages 20858-20868Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.017988
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Funding
- Burroughs Wellcome Fund
- Wellcome Trust
- National Institutes of Health (NIAID)
- U.S. Department of Defense
- Military Infectious Diseases Research Program
- French Institut National de la Sante et de la Recherche Medicale (Inserm)
- European Commission
- Novartis Institute for Tropical Diseases (NITD, Singapore)
- Medical Research Council
- Medical Research Council [G0501670] Funding Source: researchfish
- MRC [G0501670] Funding Source: UKRI
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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.
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