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

التفاصيل البيبلوغرافية
العنوان: Plasmodium NEK1 coordinates MTOC organisation and kinetochore attachment during rapid mitosis in male gamete formation
المؤلفون: Zeeshan, Mohammad, Rashpa, Ravish, Ferguson, David J, Mckeown, George, Nugmanova, Raushan, Subodhi, Amit K., Beyeler, Raphael, Pashley, Sarah L, Markus, Robert, Brady, Declan, Roques, Magali, Bottrill, Andrew R, Fry, Andrew M, Pain, Arnab, vaughan, sue, Holder, Anthony A, Tromer, Eelco C., Brochet, Mathieu, Tewari, Rita
المساهمون: Pathogen Genomics Group, Bioscience Program, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia, Bioscience Program, Biological and Environmental Science and Engineering (BESE) Division, University of Oxford, OX2 6GG, Oxford, England, University of Geneva, Faculty of Medicine, Geneva, Switzerland, Oxford Brookes University, Department of Biological and Medical Sciences, Oxford,UK, University of Oxford, John Radcliffe Hospital, Nuffield Department of Clinical Laboratory Science, Oxford, United Kingdom., Institute of Cell Biology, University of Bern, Bern, Switzerland., School of Life Sciences, Gibbet Hill Campus, University of Warwick, Coventry, UK, Department of Molecular and Cell Biology, University of Leicester, Leicester, UK, Malaria Parasitology Laboratory, The Francis Crick Institute, London, UK, Cell Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, Faculty of Science and Engineering, University of Groningen, Groningen, The Netherlands
بيانات النشر: Cold Spring Harbor Laboratory
سنة النشر: 2024
المجموعة: King Abdullah University of Science and Technology: KAUST Repository
الوصف: 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, 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 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 eight minutes followed by karyokinesis to generate haploid gametes. Our previous Plasmodium kinome screen identified four Nek genes, of which two, 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 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 Plasmodium NEK1 kinase is an important component of MTOC organisation and essential regulator of chromosome segregation during male gamete formation. ; This work was supported by: ERC advance grant funded by UKRI Frontier Science (EP/X024776/1), MRC UK (G0900278, MR/K011782/1, MR/N023048/1) and BBSRC (BB/N017609/1) to RT; the Francis Crick Institute (FC001097), the Cancer Research UK (FC001097), the UK Medical ...
نوع الوثيقة: report
وصف الملف: application/pdf
اللغة: unknown
Relation: http://hdl.handle.net/10754/697069
DOI: 10.1101/2024.02.05.578160
الاتاحة: http://hdl.handle.net/10754/697069
https://doi.org/10.1101/2024.02.05.578160
Rights: This is a preprint version of a paper and has not been peer reviewed. Archived with thanks to Cold Spring Harbor Laboratory.
رقم الانضمام: edsbas.E1557C69
قاعدة البيانات: BASE
الوصف
DOI:10.1101/2024.02.05.578160