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Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
Published on: September 20, 2019
Plasmodium ARK1 regulates spindle formation during atypical mitosis and forms a divergent chromosomal passenger
Rita Tewari1, Annu Nagar2, Ryuji Yanase1
1University of Nottingham.
Abstract:
Mitosis in Plasmodium spp., the causative agent of malaria, is fundamentally different from model eukaryotes, proceeding via a bipartite microtubule organising centre (MTOC) and lacking canonical regulators such as Polo and Bub1 kinases. During schizogony, asynchronous nuclear replication produces a multinucleate schizont, while rapid male gametogony generates an octaploid nucleus before gamete formation. Here, we identify Aurora-related kinase 1 (ARK1) as a key component of inner MTOC and spindle formation, controlling kinetochore dynamics and driving mitotic progression. Conditional ARK1 depletion disrupts spindle biogenesis, kinetochore segregation, karyokinesis and cytokinesis in both stages, and affects parasite transmission. Interactome analysis reveals ARK1 as the catalytic core of a non-canonical chromosomal passenger complex (CPC) containing two divergent inner centromere proteins (INCENPs) but lacking Survivin and Borealin. Comparative genomics indicates this CPC architecture arose early in Apicomplexa, replacing canonical centromere-targeting modules. These findings uncover a distinct mitotic machinery in Plasmodium and identify the ARK1-INCENP interface as a potential multistage target for malaria therapeutic intervention.
Insights
Malaria-causing Plasmodium parasites have unique mitosis. Aurora-related kinase 1 (ARK1) is crucial for spindle formation and segregation, offering a potential therapeutic target.
Area of Science:
- Cell Biology
- Parasitology
- Molecular Biology
Background:
- Mitosis in Plasmodium differs from model eukaryotes, lacking key regulators.
- Plasmodium exhibits unique nuclear replication during schizogony and gametogony.
Purpose of the Study:
- To identify key regulators of Plasmodium mitosis.
- To investigate the role of Aurora-related kinase 1 (ARK1) in parasite cell division.
- To characterize the Plasmodium chromosomal passenger complex (CPC).
Main Methods:
- Conditional depletion of ARK1.
- Interactome analysis to identify ARK1 binding partners.
- Comparative genomics within Apicomplexa.
Main Results:
- ARK1 is essential for inner MTOC and spindle formation, controlling kinetochore dynamics.
- ARK1 depletion disrupts spindle biogenesis, segregation, and cytokinesis, impacting parasite transmission.
- ARK1 forms a non-canonical CPC with two INCENPs, lacking Survivin and Borealin.
Conclusions:
- Plasmodium utilizes a distinct mitotic machinery.
- The ARK1-INCENP complex is a conserved feature in Apicomplexa.
- The ARK1-INCENP interface represents a potential therapeutic target for malaria.
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