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

Abstract

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.

• Authors: Luc Reininger, Oliver Billker, Rita Tewari, Arunima Mukhopadhyay, Clare Fennell, Dominique Dorin-Semblat, Caroline Doerig, Dean Goldring, Leonie Harmse, Lisa Ranford-Cartwright, Jeremy Packer, Christian Doerig
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 280 Issue 36 Pg. 31957-64 (Sep 09 2005) ISSN: 0021-9258 [Print] United States
• PMID: 15970588 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Protozoan Proteins
• RNA, Messenger
• Protein Kinases
• NIMA-Related Kinases
• NIMA-related kinase 4, Plasmodium falciparum
• Protein Serine-Threonine Kinases

Topics

• 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