@article{471589791a404692a3feee3d827c915f,
title = "Plasmodium ARK2 and EB1 drive unconventional spindle dynamics, during chromosome segregation in sexual transmission stages",
abstract = "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.",
author = "Mohammad Zeeshan and Edward Rea and Steven Abel and Kruno Vuku{\v s}i{\'c} and Robert Markus and Declan Brady and Antonius Eze and Ravish Rashpa and Balestra, {Aurelia C.} and Bottrill, {Andrew R.} and Mathieu Brochet and Guttery, {David S.} and Toli{\'c}, {Iva M.} and Holder, {Anthony A.} and {Le Roch}, {Karine G.} and Tromer, {Eelco C.} and Rita Tewari",
note = "Funding Information: This work was supported by grants from: ERC advance grant funded by UKRI Frontier Science (EP/X024776/1), MRC UK (G0900109, G0900278, MR/K011782/1) and BBSRC (BB/N017609/1, BB/L013827/1) to R.T. M.Z. was supported by BBSRC (BB/N017609/1) and (EP/X024776/1). The Francis Crick Institute (FC001097), which receives its core funding from Cancer Research UK (FC001097), the UK Medical Research Council (FC001097), and the Wellcome Trust (FC001097) to A.A.H.; the NIH/NIAID (R01 AI136511) and the University of California, Riverside (NIFA-Hatch-225935) to KGLR; E.T. is supported by a personal fellowship from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek, the Netherlands (grant no. VI.Veni.202.223); Swiss National Science Foundation (31003A_179321 and 310030_208151) to M.B. and R.R. I.M.T. and K.V. acknowledge support by the European Research Council (ERC Synergy Grant, GA Number 855158, granted to IMT), and projects co-financed by the Croatian Government and European Union through the European Regional Development Fund—the Competitiveness and Cohesion Operational Program: IPSted (grant KK.01.1.1.04.0057) and QuantiXLie Center of Excellence (grant KK.01.1.1.01.0004). AE was supported by a Commonwealth Academic Fellowship awarded by the Commonwealth Scholarship Commission in the UK. For Open Access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. We thank Julie Rodgers for helping to maintain the insectary and other technical works and Cleidiane Zampronio at Warwick University for mass spectrometry methods. Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",
year = "2023",
month = sep,
day = "13",
doi = "10.1038/s41467-023-41395-3",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}