Journal article
Disruption of Plasmodium falciparum kinetochore proteins destabilises the nexus between the centrosome equivalent and the mitotic apparatus
J Li, GJ Shami, B Liffner, E Cho, F Braet, MT Duraisingh, S Absalon, MWA Dixon, L Tilley
Nature Communications | NATURE PORTFOLIO | Published : 2024
Abstract
Plasmodium falciparum is the causative agent of malaria and remains a pathogen of global importance. Asexual blood stage replication, via a process called schizogony, is an important target for the development of new antimalarials. Here we use ultrastructure-expansion microscopy to probe the organisation of the chromosome-capturing kinetochores in relation to the mitotic spindle, the centriolar plaque, the centromeres and the apical organelles during schizont development. Conditional disruption of the kinetochore components, PfNDC80 and PfNuf2, is associated with aberrant mitotic spindle organisation, disruption of the centromere marker, CENH3 and impaired karyokinesis. Surprisingly, kinetoc..
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Grants
Awarded by University of Nottingham
Funding Acknowledgements
We thank Professor Rita Tewari, the University of Nottingham, UK and Professor Jing Yuan, Xiamen University, China, for advice. We acknowledge the facilities at the Biological Optical Microscopy Platform and the Flow Cytometry Platform, The University of Melbourne, the Microscopy Resources on the North Quad (MicRoN) core at Harvard Medical School, and the University of Sydney Microscopy & Microanalysis facilities of Microscopy Australia. For research support, we thank the Australian Research Council (FL150100106 to L.T.), the National Health and Medical Research Council of Australia (APP1098992 to L.T.) and the NIH (5R01AI167570 to M.T.D). B.L. is supported by an American Heart Association Postdoctoral Fellowship (23POST1011626).