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Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle

View ORCID ProfileMohammad Zeeshan, View ORCID ProfileRavish Rashpa, View ORCID ProfileDavid J Ferguson, Steven Abel, Zeinab Chahine, View ORCID ProfileDeclan Brady, View ORCID ProfileSue Vaughan, View ORCID ProfileCarolyn A. Moores, View ORCID ProfileKarine G. Le Roch, View ORCID ProfileMathieu Brochet, View ORCID ProfileAnthony A. Holder, View ORCID ProfileRita Tewari
doi: https://doi.org/10.1101/2021.05.26.445751
Mohammad Zeeshan
1University of Nottingham, School of Life Sciences, Nottingham, United Kingdom
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  • For correspondence: rita.tewari@nottingham.ac.uk zeeshanmf@gmail.com
Ravish Rashpa
2University of Geneva, Faculty of Medicine, Geneva, Switzerland
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David J Ferguson
3Oxford Brookes University, Department of Biological and Medical Sciences, Oxford, United Kingdom
4University of Oxford, John Radcliffe Hospital, Nuffield Department of Clinical Laboratory Science, Oxford, United Kingdom
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Steven Abel
5Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave., Riverside, USA
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Zeinab Chahine
5Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave., Riverside, USA
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Declan Brady
1University of Nottingham, School of Life Sciences, Nottingham, United Kingdom
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Sue Vaughan
3Oxford Brookes University, Department of Biological and Medical Sciences, Oxford, United Kingdom
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Carolyn A. Moores
6Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, London, United Kingdom
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Karine G. Le Roch
5Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave., Riverside, USA
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Mathieu Brochet
2University of Geneva, Faculty of Medicine, Geneva, Switzerland
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Anthony A. Holder
7The Francis Crick Institute, Malaria Parasitology Laboratory, London, United Kingdom
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Rita Tewari
1University of Nottingham, School of Life Sciences, Nottingham, United Kingdom
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  • ORCID record for Rita Tewari
  • For correspondence: rita.tewari@nottingham.ac.uk zeeshanmf@gmail.com
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Abstract

Kinesins are microtubule-based motors important in cell division, motility, polarity, and intracellular transport in many eukaryotes. However, they are poorly studied in the divergent eukaryotic pathogens- Plasmodium spp., the causative agents of malaria, which manifest atypical aspects of cell division and plasticity of morphology throughout the lifecycle in both mammalian and mosquito hosts. Here we describe a genome-wide screen of Plasmodium kinesins, revealing diverse subcellular locations and functions in spindle assembly, axoneme formation and cell morphology. Surprisingly, only kinesin-13 is essential for growth in the mammalian host while the other eight kinesins are required during the proliferative and invasive stages of parasite transmission through the mosquito vector. In-depth analyses of kinesin-13 and kinesin-20 revealed functions in microtubule dynamics during apical cell polarity formation, spindle assembly, and axoneme biogenesis. These findings help us to understand the importance of microtubule motors and may be exploited to discover new therapeutic interventions against malaria.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • 1. Title has been changed 2. Minor changes in manuscript 3. Figures have been updated 4. Additional figures have been added in supplementary

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Posted June 15, 2022.
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Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle
Mohammad Zeeshan, Ravish Rashpa, David J Ferguson, Steven Abel, Zeinab Chahine, Declan Brady, Sue Vaughan, Carolyn A. Moores, Karine G. Le Roch, Mathieu Brochet, Anthony A. Holder, Rita Tewari
bioRxiv 2021.05.26.445751; doi: https://doi.org/10.1101/2021.05.26.445751
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Genome-wide functional analysis reveals key roles for kinesins in the mammalian and mosquito stages of the malaria parasite life cycle
Mohammad Zeeshan, Ravish Rashpa, David J Ferguson, Steven Abel, Zeinab Chahine, Declan Brady, Sue Vaughan, Carolyn A. Moores, Karine G. Le Roch, Mathieu Brochet, Anthony A. Holder, Rita Tewari
bioRxiv 2021.05.26.445751; doi: https://doi.org/10.1101/2021.05.26.445751

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