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Plasmodium ARK2 and EB1 drive unconventional spindle dynamics, during chromosome segregation in sexual transmission stages

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posted on 2023-12-04, 09:14 authored by M Zeeshan, E Rea, S Abel, K Vukušić, R Markus, D Brady, A Eze, R Rashpa, AC Balestra, AR Bottrill, M Brochet, DS Guttery, IM Tolić, AA Holder, KG Le Roch, EC Tromer, R Tewari

The Aurora family of kinases orchestrates chromosome segregation and cytokinesis during cell division, with precise spatiotemporal regulation of its catalytic activities by distinct protein scaffolds. Plasmodium spp., the causative agents of malaria, are unicellular eukaryotes with three unique and highly divergent aurora-related kinases (ARK1-3) that are essential for asexual cellular proliferation but lack most canonical scaffolds/activators. Here we investigate the role of ARK2 during sexual proliferation of the rodent malaria Plasmodium berghei, using a combination of super-resolution microscopy, mass spectrometry, and live-cell fluorescence imaging. We find that ARK2 is primarily located at spindle microtubules in the vicinity of kinetochores during both mitosis and meiosis. Interactomic and co-localisation studies reveal several putative ARK2-associated interactors including the microtubule-interacting protein EB1, together with MISFIT and Myosin-K, but no conserved eukaryotic scaffold proteins. Gene function studies indicate that ARK2 and EB1 are complementary in driving endomitotic division and thereby parasite transmission through the mosquito. This discovery underlines the flexibility of molecular networks to rewire and drive unconventional mechanisms of chromosome segregation in the malaria parasite.

History

Author affiliation

Department of Genetics and Genome Biology, University of Leicester

Version

  • VoR (Version of Record)

Published in

Nature Communications

Volume

14

Issue

1

Pagination

5652

Publisher

Springer Science and Business Media LLC

issn

2041-1723

eissn

2041-1723

Copyright date

2023

Available date

2023-12-04

Spatial coverage

England

Language

eng

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