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.

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
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

Av författaren/redakt...: Reininger, Luc; Billker, Oliver; Tewari, Rita; Mukhopadhyay, Ar ...; Fennell, Clare; Dorin-Semblat, D ...; visa fler...; Doerig, Caroline; Goldring, Dean; Harmse, Leonie; Ranford-Cartwrig ...; Packer, Jeremy; Doerig, Christia ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

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