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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

Amino Acid Sequence

Animals

Animals

Genetically Modified

Cell Cycle Proteins/*metabolism

Culicidae/parasitology

DNA Replication

Erythrocytes/parasitology

Gene Expression Profiling

Gene Targeting

Green Fluorescent Proteins/metabolism

Humans

Life Cycle Stages

Malaria

Falciparum/*enzymology/parasitology/transmission

Meiosis

Molecular Sequence Data

NIMA-Related Kinase 1

Parasites/enzymology/genetics/growth & development

Phenotype

Plasmodium berghei/cytology/*enzymology/growth & development

Plasmodium falciparum/*enzymology/genetics/growth & development

Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism

Protozoan Proteins/genetics/*metabolism

RNA

Messenger/genetics/metabolism

Recombinant Fusion Proteins/metabolism

Sequence Alignment

*Sexual Development

Publication and Content Type

ref (subject category)

art (subject category)