Plasmodium ARK1 regulates spindle formation during atypical mitosis and forms a divergent chromosomal passenger complex

Year: 2026

Type: article

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 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 shows that ARK1 forms the catalytic core of a non-canonical chromosomal passenger complex (CPC) containing two highly divergent inner centromere proteins (INCENPs), which we term INCENP-A and INCENP-B, and lacking the canonical chromatin-targeting subunits Survivin and Borealin. Comparative genomics suggests that apicomplexan INCENPs arose through recurrent lineage-specific duplications, reflecting an evolutionary rewiring of CPC architecture in this eukaryotic lineage. Together, these findings reveal key adaptations in Plasmodium mitosis involving ARK1 and its INCENP scaffolds, and identify the ARK1-INCENP interface as a potential multistage target for antimalarial intervention.

Source: Nature Communications

DOI: 10.1038/s41467-026-69460-7

Authors: Annu Nagar, Ryuji Yanase, Mohammad Zeeshan, David J. P. Ferguson, Steven Abel, Sarah L. Pashley, Akancha Mishra, Anthonius Eze, Edward Rea, Declan Brady, Andrew R. Bottrill, Sue Vaughan, Karine G. Le Roch, David S. Guttery, Anthony A. Holder, Eelco C. Tromer, Pushkar Sharma, Rita Tewari

Institutions: National Institute of Immunology, University of Nottingham, Central Drug Research Institute, Oxford Brookes University, University of California, Riverside, University of Warwick, The Francis Crick Institute, University of Groningen

Language: English

Topic: Microtubule and mitosis dynamics

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: Wellcome Trust, Francis Crick Institute, UK Research and Innovation, Cancer Research UK, University of Warwick, Commonwealth Scholarship Commission, Department of Biotechnology, Ministry of Science and Technology, India, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, The Wellcome Trust DBT India Alliance, National Institute of Immunology, National Institutes of Health, National Institute of Food and Agriculture, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Institute of Allergy and Infectious Diseases, Common Fund

OpenAlex ID: W7131641820