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

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 organis...

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Veröffentlicht in:	Nature communications Jg. 15; H. 1; S. 5794 - 16
Hauptverfasser:	Li, Jiahong, Shami, Gerald J., Liffner, Benjamin, Cho, Ellie, Braet, Filip, Duraisingh, Manoj T., Absalon, Sabrina, Dixon, Matthew W. A., Tilley, Leann
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 10.07.2024 Nature Publishing Group Nature Portfolio
Schlagworte:	14/19 14/28 14/34 14/35 14/63 42/109 631/326/421 631/80/641/1655 Centromere - metabolism Centromeres Centrosome - metabolism Developmental stages Disruption Equivalence Humanities and Social Sciences Humans Kinetochores Kinetochores - metabolism Malaria Malaria, Falciparum - metabolism Malaria, Falciparum - parasitology Merozoites Merozoites - metabolism Merozoites - physiology Microscopy Mitosis multidisciplinary Nuclear Envelope - metabolism Nuclei Organelles Parasites Plasmodium falciparum Plasmodium falciparum - metabolism Plasmodium falciparum - physiology Protozoan Proteins - genetics Protozoan Proteins - metabolism Schizogony Science Science (multidisciplinary) Spindle Apparatus - metabolism Ultrastructure Vector-borne diseases
ISSN:	2041-1723, 2041-1723
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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, Pf NDC80 and Pf Nuf2, 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. Using Ultra-Expansion Microscopy of the malaria parasite, P. falciparum , Li et al. show that disruption of kinetochore components breaks a nexus between the mitotic spindle and the nascent apical organelles.
AbstractList	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, Pf NDC80 and Pf Nuf2, 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. 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. Using Ultra-Expansion Microscopy of the malaria parasite, P. falciparum, Li et al. show that disruption of kinetochore components breaks a nexus between the mitotic spindle and the nascent apical organelles. 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. 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, 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. 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.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. 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, Pf NDC80 and Pf Nuf2, 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. Using Ultra-Expansion Microscopy of the malaria parasite, P. falciparum , Li et al. show that disruption of kinetochore components breaks a nexus between the mitotic spindle and the nascent apical organelles.
ArticleNumber	5794
Author	Tilley, Leann Liffner, Benjamin Braet, Filip Cho, Ellie Duraisingh, Manoj T. Absalon, Sabrina Shami, Gerald J. Li, Jiahong Dixon, Matthew W. A.
Author_xml	– sequence: 1 givenname: Jiahong orcidid: 0000-0002-9687-0101 surname: Li fullname: Li, Jiahong organization: Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health – sequence: 2 givenname: Gerald J. orcidid: 0000-0003-2094-1740 surname: Shami fullname: Shami, Gerald J. organization: School of Medical Sciences (Molecular and Cellular Biomedicine) & Australian Centre for Microscopy and Microanalysis, The University of Sydney – sequence: 3 givenname: Benjamin orcidid: 0000-0002-1573-6139 surname: Liffner fullname: Liffner, Benjamin organization: Department of Pharmacology and Toxicology, Indiana University School of Medicine – sequence: 4 givenname: Ellie orcidid: 0000-0002-2932-1890 surname: Cho fullname: Cho, Ellie organization: Biological Optical Microscopy Platform, The University of Melbourne – sequence: 5 givenname: Filip surname: Braet fullname: Braet, Filip organization: School of Medical Sciences (Molecular and Cellular Biomedicine) & Australian Centre for Microscopy and Microanalysis, The University of Sydney – sequence: 6 givenname: Manoj T. orcidid: 0000-0001-8534-5515 surname: Duraisingh fullname: Duraisingh, Manoj T. organization: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health – sequence: 7 givenname: Sabrina surname: Absalon fullname: Absalon, Sabrina organization: Department of Pharmacology and Toxicology, Indiana University School of Medicine – sequence: 8 givenname: Matthew W. A. orcidid: 0000-0001-9732-9686 surname: Dixon fullname: Dixon, Matthew W. A. email: matthew.dixon@unimelb.edu.au organization: Department of Infectious Diseases, The Peter Doherty Institute, The University of Melbourne, Walter and Eliza Hall Institute – sequence: 9 givenname: Leann orcidid: 0000-0001-9910-0199 surname: Tilley fullname: Tilley, Leann email: ltilley@unimelb.edu.au organization: Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
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Snippet	Plasmodium falciparum is the causative agent of malaria and remains a pathogen of global importance. Asexual blood stage replication, via a process called... Plasmodium falciparum is the causative agent of malaria and remains a pathogen of global importance. Asexual blood stage replication, via a process called... Abstract Plasmodium falciparum is the causative agent of malaria and remains a pathogen of global importance. Asexual blood stage replication, via a process...
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SubjectTerms	14/19 14/28 14/34 14/35 14/63 42/109 631/326/421 631/80/641/1655 Centromere - metabolism Centromeres Centrosome - metabolism Developmental stages Disruption Equivalence Humanities and Social Sciences Humans Kinetochores Kinetochores - metabolism Malaria Malaria, Falciparum - metabolism Malaria, Falciparum - parasitology Merozoites Merozoites - metabolism Merozoites - physiology Microscopy Mitosis multidisciplinary Nuclear Envelope - metabolism Nuclei Organelles Parasites Plasmodium falciparum Plasmodium falciparum - metabolism Plasmodium falciparum - physiology Protozoan Proteins - genetics Protozoan Proteins - metabolism Schizogony Science Science (multidisciplinary) Spindle Apparatus - metabolism Ultrastructure Vector-borne diseases
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Title	Disruption of Plasmodium falciparum kinetochore proteins destabilises the nexus between the centrosome equivalent and the mitotic apparatus
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