Plasmodium kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
17
03
2019
accepted:
26
08
2019
entrez:
11
10
2019
pubmed:
11
10
2019
medline:
15
2
2020
Statut:
epublish
Résumé
Kinesin-8 proteins are microtubule motors that are often involved in regulation of mitotic spindle length and chromosome alignment. They move towards the plus ends of spindle microtubules and regulate the dynamics of these ends due, at least in some species, to their microtubule depolymerization activity. Plasmodium spp. exhibit an atypical endomitotic cell division in which chromosome condensation and spindle dynamics in the different proliferative stages are not well understood. Genome-wide shared orthology analysis of Plasmodium spp. revealed the presence of two kinesin-8 motor proteins, kinesin-8X and kinesin-8B. Here we studied the biochemical properties of kinesin-8X and its role in parasite proliferation. In vitro, kinesin-8X has motility and depolymerization activities like other kinesin-8 motors. To understand the role of Plasmodium kinesin-8X in cell division, we used fluorescence-tagging and live cell imaging to define its location, and gene targeting to analyse its function, during all proliferative stages of the rodent malaria parasite P. berghei life cycle. The results revealed a spatio-temporal involvement of kinesin-8X in spindle dynamics and an association with both mitotic and meiotic spindles and the putative microtubule organising centre (MTOC). Deletion of the kinesin-8X gene revealed a defect in oocyst development, confirmed by ultrastructural studies, suggesting that this protein is required for oocyst development and sporogony. Transcriptome analysis of Δkinesin-8X gametocytes revealed modulated expression of genes involved mainly in microtubule-based processes, chromosome organisation and the regulation of gene expression, supporting a role for kinesin-8X in cell division. Kinesin-8X is thus required for parasite proliferation within the mosquito and for transmission to the vertebrate host.
Identifiants
pubmed: 31600347
doi: 10.1371/journal.ppat.1008048
pii: PPATHOGENS-D-19-00520
pmc: PMC6786531
doi:
Substances chimiques
Protozoan Proteins
0
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008048Subventions
Organisme : Cancer Research UK
ID : FC001097
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001097
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N017609/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001097
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N023048/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0900278
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K011782/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104196/Z/14/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0900109
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI136511
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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