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

Autor: Zeeshan M; University of Nottingham, School of Life Sciences, Nottingham, United Kingdom., Rashpa R; University of Geneva, Faculty of Medicine, Geneva, Switzerland., Ferguson DJ; Oxford Brookes University, Department of Biological and Medical Sciences, Oxford, United Kingdom.; University of Oxford, John Radcliffe Hospital, Nuffield Department of Clinical Laboratory Science, Oxford, United Kingdom., Mckeown G; University of Nottingham, School of Life Sciences, Nottingham, United Kingdom., Nugmanova R; Pathogen Genomics Group, Bioscience Program, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia., Subudhi AK; Pathogen Genomics Group, Bioscience Program, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia., Beyeler R; Institute of Cell Biology, University of Bern, Bern, Switzerland., Pashley SL; University of Nottingham, School of Life Sciences, Nottingham, United Kingdom., Markus R; University of Nottingham, School of Life Sciences, Nottingham, United Kingdom., Brady D; University of Nottingham, School of Life Sciences, Nottingham, United Kingdom., Roques M; Institute of Cell Biology, University of Bern, Bern, Switzerland., Bottrill AR; School of Life Sciences, Gibbet Hill Campus, University of Warwick, Coventry, United Kingdom., Fry AM; Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom., Pain A; Pathogen Genomics Group, Bioscience Program, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia., Vaughan S; Oxford Brookes University, Department of Biological and Medical Sciences, Oxford, United Kingdom., Holder AA; Malaria Parasitology Laboratory, The Francis Crick Institute, London, United Kingdom., Tromer EC; Cell Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands., Brochet M; University of Geneva, Faculty of Medicine, Geneva, Switzerland., Tewari R; University of Nottingham, School of Life Sciences, Nottingham, United Kingdom.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2024 Sep 10; Vol. 22 (9), pp. e3002802. Date of Electronic Publication: 2024 Sep 10 (Print Publication: 2024).
DOI: 10.1371/journal.pbio.3002802
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Zeeshan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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