An essential role for the Plasmodium Nek-2 Nima-related protein kinase in the sexual development of malaria parasites.

Abstract

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.

• Authors: Luc Reininger, Rita Tewari, Clare Fennell, Zoe Holland, Dean Goldring, Lisa Ranford-Cartwright, Oliver Billker, Christian Doerig
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 31 Pg. 20858-68 (Jul 31 2009) ISSN: 1083-351X [Electronic] United States
• PMID: 19491095 (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.)

Chemical References

• Cell Cycle Proteins
• Protozoan Proteins
• RNA, Messenger
• Recombinant Fusion Proteins
• Green Fluorescent Proteins
• NEK1 protein, human
• NIMA-Related Kinase 1
• Protein Serine-Threonine Kinases

Topics

• 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