A NIMA-related protein kinase is essential for completion of the sexual cycle of malaria parasites

• The molecular mechanisms regulating the sexual development of malaria parasites from gametocytes to oocysts in their mosquito vector are still largely unexplored. In other eukaryotes, NIMA-related kinases (Neks) regulate cell cycle progression and have been implicated in the regulation of meiosis. Here, we demonstrate that Nek-4, a new Plasmodium member of the Nek family, is essential for completion of the sexual cycle of the parasite. Recombinant Plasmodium falciparum Nek-4 possesses protein kinase activity and displays substrate preferences similar to those of other Neks. Nek-4 is highly expressed in gametocytes, yet disruption of the nek-4 gene in the rodent malaria parasite P. berghei has no effect on gamete formation and subsequent fertilization. However, further differentiation of zygotes into ookinetes is abolished. Measurements of nuclear DNA content indicate that zygotes lacking Nek-4 fail to undergo the genome replication to the tetraploid level that precedes meiosis. Cell cycle progression in the zygote is identified as a likely precondition for its morphological transition to the ookinete and for the successful establishment of a malaria infection in the mosquito.

Ämnesord

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

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

Nyckelord

Amino Acid Sequence

Animals

Catalytic Domain

Cell Cycle/*physiology

DNA Replication/physiology

Evolution

Molecular

Humans

Life Cycle Stages/*physiology

Meiosis/physiology

Molecular Sequence Data

NIMA-Related Kinases

Phylogeny

Plasmodium falciparum/*enzymology/genetics/*growth & development

Protein Kinases/genetics/*physiology

Protein-Serine-Threonine Kinases

Protozoan Proteins/genetics/*physiology

RNA

Messenger/metabolism

Sequence Alignment

Publikations- och innehållstyp

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