title: An essential Aurora-related kinase transiently associates with spindle pole bodies during Plasmodium falciparum erythrocytic schizogony.
abstract: Aurora kinases compose a family of conserved Ser/Thr protein kinases playing essential roles in eukaryotic cell division. To date, Aurora homologues remain uncharacterized in the protozoan phylum Apicomplexa. In malaria parasites, the characterization of Aurora kinases may help understand the cell cycle control during erythrocytic schizogony where asynchronous nuclear divisions occur. In this study, we revisited the kinome of Plasmodium falciparum and identified three Aurora-related kinases, Pfark-1, -2, -3. Among these, Pfark-1 is highly conserved in malaria parasites and also appears to be conserved across Apicomplexa. By tagging the endogenous Pfark-1 gene with the green fluorescent protein (GFP) in live parasites, we show that the Pfark-1-GFP protein forms paired dots associated with only a subset of nuclei within individual schizonts. Immunofluorescence analysis using an anti-α-tubulin antibody strongly suggests a recruitment of Pfark-1 at duplicated spindle pole bodies at the entry of the M phase of the cell cycle. Unsuccessful attempts at disrupting the Pfark-1 gene with a knockout construct further indicate that Pfark-1 is required for parasite growth in red blood cells. Our study provides new insights into the cell cycle control of malaria parasites and reports the importance of Aurora kinases as potential targets for new antimalarials.
authors.affiliation: INSERM-EPFL Joint Laboratory, Global Health Institute, EPFL-SV-GHI, Station 19, CH-1015 Lausanne, Switzerland. luc.reininger@epfl.ch
authors.forename: Luc
authors.initials: L
authors.lastname: Reininger
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Wilkes
authors.forename: Hélène
authors.initials: H
authors.lastname: Bourgade
authors.forename: Diego
authors.initials: D
authors.lastname: Miranda-Saavedra
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
mesh_terms: D064127:Aurora Kinases; D017124:Conserved Sequence; D004912:Erythrocytes / Q000469:parasitology*; D017353:Gene Deletion; D020043:Genes, Essential; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases