Plasmodium NEK1 coordinates MTOC organisation and kinetochore attachment during rapid mitosis in male gamete formation

Mitosis is an important process in the cell cycle required for cells to divide. Never in mitosis (NIMA)-like kinases (NEKs) are regulators of mitotic functions in diverse organisms. Plasmodium spp., the causative agent of malaria is a divergent unicellular haploid eukaryote with some unusual features in terms of its mitotic and nuclear division cycle that presumably facilitate proliferation in varied environments. For example, during the sexual stage of male gametogenesis that occurs within the mosquito host, an atypical rapid closed endomitosis is observed. Three rounds of genome replication from 1N to 8N and successive cycles of multiple spindle formation and chromosome segregation occur within 8 min followed by karyokinesis to generate haploid gametes. Our previous Plasmodium berghei kinome screen identified 4 Nek genes, of which 2, NEK2 and NEK4, are required for meiosis. NEK1 is likely to be essential for mitosis in asexual blood stage schizogony in the vertebrate host, but its function during male gametogenesis is unknown. Here, we study NEK1 location and function, using live cell imaging, ultrastructure expansion microscopy (U-ExM), and electron microscopy, together with conditional gene knockdown and proteomic approaches. We report spatiotemporal NEK1 location in real-time, coordinated with microtubule organising centre (MTOC) dynamics during the unusual mitoses at various stages of the Plasmodium spp. life cycle. Knockdown studies reveal NEK1 to be an essential component of the MTOC in male cell differentiation, associated with rapid mitosis, spindle formation, and kinetochore attachment. These data suggest that P. berghei NEK1 kinase is an important component of MTOC organisation and essential regulator of chromosome segregation during male gamete formation.

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Journal
PLoS Biology
Published
2024-09-10
DOI
https://doi.org/10.1371/journal.pbio.3002802
Citations
17
Primary Topic
Malaria Research and Control
Type
article
Field-Weighted Citation Impact
9.23

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article

Plasmodium NEK1 coordinates MTOC organisation and kinetochore attachment during rapid mitosis in male gamete formation

Declan Brady, Raphael Beyeler, Andrew R. Bottrill, Arnab Pain et al.
17 citations
PLoS Biology
Malaria Research and Control
9.23
article

Plasmodium NEK1 coordinates MTOC organisation and kinetochore attachment during rapid mitosis in male gamete formation

Declan Brady, Raphael Beyeler, Andrew R. Bottrill, Arnab Pain, Andrew M. Fry, Róbert Márkus, Amit Kumar Subudhi, Eelco C. Tromer, Mohammad Zeeshan, Raushan Nugmanova, Rita Tewari, Sarah L. Pashley, David Ferguson, Magali Roques, Anthony A. Holder, Ravish Rashpa, Sue Vaughan, Mathieu Brochet, George Mckeown
article en
17 citations

Abstract

Mitosis is an important process in the cell cycle required for cells to divide. Never in mitosis (NIMA)-like kinases (NEKs) are regulators of mitotic functions in diverse organisms. Plasmodium spp., the causative agent of malaria is a divergent unicellular haploid eukaryote with some unusual features in terms of its mitotic and nuclear division cycle that presumably facilitate proliferation in varied environments. For example, during the sexual stage of male gametogenesis that occurs within the mosquito host, an atypical rapid closed endomitosis is observed. Three rounds of genome replication from 1N to 8N and successive cycles of multiple spindle formation and chromosome segregation occur within 8 min followed by karyokinesis to generate haploid gametes. Our previous Plasmodium berghei kinome screen identified 4 Nek genes, of which 2, NEK2 and NEK4, are required for meiosis. NEK1 is likely to be essential for mitosis in asexual blood stage schizogony in the vertebrate host, but its function during male gametogenesis is unknown. Here, we study NEK1 location and function, using live cell imaging, ultrastructure expansion microscopy (U-ExM), and electron microscopy, together with conditional gene knockdown and proteomic approaches. We report spatiotemporal NEK1 location in real-time, coordinated with microtubule organising centre (MTOC) dynamics during the unusual mitoses at various stages of the Plasmodium spp. life cycle. Knockdown studies reveal NEK1 to be an essential component of the MTOC in male cell differentiation, associated with rapid mitosis, spindle formation, and kinetochore attachment. These data suggest that P. berghei NEK1 kinase is an important component of MTOC organisation and essential regulator of chromosome segregation during male gamete formation.

PLoS BiologyVol. 22(9)
University of Geneva (CH), University of Bern (CH), Oxford Brookes University (GB), University of Nottingham (GB), University of Leicester (GB), University of Groningen (NL), The Francis Crick Institute (GB), John Radcliffe Hospital (GB), University of Warwick (GB), University of Oxford (GB), Science Oxford (GB), King Abdullah University of Science and Technology (SA)
National Science Foundation, Wellcome Trust, Francis Crick Institute, UK Research and Innovation, Cancer Research UK, Department of Biotechnology, Ministry of Science and Technology, India, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, King Abdullah University of Science and Technology, The Wellcome Trust DBT India Alliance, Medical Research Council, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council
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Openalex Percentile: Top 2%
Malaria Research and Control
9.23
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