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A NIMA-related protein kinase is essential for completion of the sexual cycle of malaria parasites
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2005 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 280, no 36, p. 31957-31964Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2005. Vol. 280, no 36, p. 31957-31964
Keywords [en]
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
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Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-165889DOI: 10.1074/jbc.M504523200PubMedID: 15970588OAI: oai:DiVA.org:umu-165889DiVA, id: diva2:1379345
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United States
Available from: 2019-12-17 Created: 2019-12-17 Last updated: 2019-12-19Bibliographically approved

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Billker, Oliver

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  • apa
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