Disruption of Plasmodium falciparum kinetochore proteins destabilises the nexus between the centrosome equivalent and the mitotic apparatus.

Autor: Li J; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia.; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA., Shami GJ; School of Medical Sciences (Molecular and Cellular Biomedicine) & Australian Centre for Microscopy and Microanalysis, The University of Sydney, Sydney, NSW, Australia., Liffner B; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA., Cho E; Biological Optical Microscopy Platform, The University of Melbourne, Parkville, VIC, Australia., Braet F; School of Medical Sciences (Molecular and Cellular Biomedicine) & Australian Centre for Microscopy and Microanalysis, The University of Sydney, Sydney, NSW, Australia., Duraisingh MT; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA., Absalon S; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA., Dixon MWA; Department of Infectious Diseases, The Peter Doherty Institute, The University of Melbourne, Parkville, VIC, Australia. matthew.dixon@unimelb.edu.au.; Walter and Eliza Hall Institute, Parkville, VIC, Australia. matthew.dixon@unimelb.edu.au., Tilley L; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia. ltilley@unimelb.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 10; Vol. 15 (1), pp. 5794. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1038/s41467-024-50167-6
Abstrakt: 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, kinetochore disruption also leads to disengagement of the centrosome equivalent from the nuclear envelope. Severing the connection between the nucleus and the apical complex leads to the formation of merozoites lacking nuclei. Here, we show that correct assembly of the kinetochore/spindle complex plays a previously unrecognised role in positioning the nascent apical complex in developing P. falciparum merozoites.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: