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Kinesin-8B controls basal body function and flagellum formation and is key to malaria parasite transmission

Mohammad Zeeshan, David J. P. Ferguson, Steven Abel, Alana Burrrell, Edward Rea, Declan Brady, Emilie Daniel, Michael Delves, Sue Vaughan, Anthony A. Holder, Karine G. Le Roch, Carolyn A. Moores, View ORCID ProfileRita Tewari
doi: https://doi.org/10.1101/686568
Mohammad Zeeshan
1School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK
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David J. P. Ferguson
2Department of Biological and Medical Sciences, Faculty of Health and Life Science, Oxford Brookes University, Gipsy Lane, Oxford OX3 0BP, UK
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Steven Abel
3Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave, Riverside, CA, 92521, USA
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Alana Burrrell
2Department of Biological and Medical Sciences, Faculty of Health and Life Science, Oxford Brookes University, Gipsy Lane, Oxford OX3 0BP, UK
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Edward Rea
1School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK
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Declan Brady
1School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK
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Emilie Daniel
1School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK
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Michael Delves
4London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
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Sue Vaughan
2Department of Biological and Medical Sciences, Faculty of Health and Life Science, Oxford Brookes University, Gipsy Lane, Oxford OX3 0BP, UK
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Anthony A. Holder
5Malaria Parasitology Laboratory, The Francis Crick Institute, London, NW1 1AT, UK
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Karine G. Le Roch
3Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave, Riverside, CA, 92521, USA
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Carolyn A. Moores
6Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, London, WC1E 7HX, United Kingdom
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Rita Tewari
1School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK
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  • ORCID record for Rita Tewari
  • For correspondence: rita.tewari@nottingham.ac.uk
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Abstract

Eukaryotic flagella are conserved microtubule-based organelles that drive cell motility. Plasmodium, the causative agent of malaria, has a single flagellate stage: the male gamete in the mosquito. Three rounds of endomitotic division together with an unusual mode of flagellum assembly rapidly produce eight motile gametes. These processes are tightly coordinated but their regulation is poorly understood. To understand this important developmental stage, we studied the function and location of the microtubule-based motor kinesin-8B, using gene-targeting, electron microscopy and live cell imaging. Deletion of the kinesin-8B gene showed no effect on mitosis but disrupted 9+2 axoneme assembly and flagellum formation during male gamete development and also completely ablated parasite transmission. Live cell imaging showed that kinesin-8B-GFP did not colocalise with kinetochores in the nucleus but instead revealed dynamic, cytoplasmic localisation with the basal bodies and the assembling axoneme during flagellum formation. We thus uncovered an unexpected role for kinesin-8B in parasite flagellum formation that is vital for the parasite life cycle.

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  • Few changes in text, Figure 2 legend and references

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Posted July 02, 2019.
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Kinesin-8B controls basal body function and flagellum formation and is key to malaria parasite transmission
Mohammad Zeeshan, David J. P. Ferguson, Steven Abel, Alana Burrrell, Edward Rea, Declan Brady, Emilie Daniel, Michael Delves, Sue Vaughan, Anthony A. Holder, Karine G. Le Roch, Carolyn A. Moores, Rita Tewari
bioRxiv 686568; doi: https://doi.org/10.1101/686568
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Kinesin-8B controls basal body function and flagellum formation and is key to malaria parasite transmission
Mohammad Zeeshan, David J. P. Ferguson, Steven Abel, Alana Burrrell, Edward Rea, Declan Brady, Emilie Daniel, Michael Delves, Sue Vaughan, Anthony A. Holder, Karine G. Le Roch, Carolyn A. Moores, Rita Tewari
bioRxiv 686568; doi: https://doi.org/10.1101/686568

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