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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
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

Ingår i:Journal of Biological Chemistry: American Society for Biochemistry and Molecular Biology284:31, s. 20858-208680021-92581083-351X

Av författaren/redakt...: Reininger, Luc; Tewari, Rita; Fennell, Clare; Holland, Zoe; Goldring, Dean; Ranford-Cartwrig ...; visa fler...; Billker, Oliver; Doerig, Christia ...; visa färre...

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