Plasmodium kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission
| Autor: | Anthony A. Holder, Rebecca R. Stanway, Declan Brady, Tobias Mourier, David J. P. Ferguson, Rita Tewari, Steven Abel, Arnab Pain, Tianyang Liu, Edward Rea, Magali Roques, Karine G. Le Roch, Fiona Shilliday, Emilie Daniel, Mohammad Zeeshan, Carolyn A. Moores, Desiree Williams, Anthony J. Roberts |
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| Přispěvatelé: | Gubbels, Marc-Jan |
| Rok vydání: | 2019 |
| Předmět: |
Male
Life Cycles Plasmodium Cell division Protozoan Proteins Kinesins Gametocytes Biochemistry Microtubules Mice 0302 clinical medicine Animal Cells Chromosome Segregation Medicine and Health Sciences Biology (General) Inbred BALB C Mice Inbred BALB C 0303 health sciences 030302 biochemistry & molecular biology Microtubule Motors Kinesin 3. Good health Cell biology Infectious Diseases Sporozoites Medical Microbiology Premature chromosome condensation Female Cellular Types Research Article QH301-705.5 Parasitic Life Cycles 1.1 Normal biological development and functioning Motor Proteins Immunology Mitosis Spindle Apparatus macromolecular substances Biology Microbiology Motor protein 03 medical and health sciences Rare Diseases Molecular Motors Underpinning research Microtubule Virology Parasite Groups parasitic diseases Parasitic Diseases Genetics Animals Molecular Biology 030304 developmental biology Oocysts Biology and Life Sciences Proteins Microtubule organizing center Cell Biology RC581-607 Malaria Spindle apparatus Vector-Borne Diseases Cytoskeletal Proteins Germ Cells Parasitology Immunologic diseases. Allergy Apicomplexa 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | PLoS pathogens, vol 15, iss 10 PLoS Pathogens, Vol 15, Iss 10, p e1008048 (2019) PLoS Pathogens |
| ISSN: | 1553-7374 |
| Popis: | 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. Author summary Kinesins are microtubule-based motors that play key roles in intracellular transport, cell division and motility. Members of the kinesin-8 family contribute to chromosome alignment during cell division in many eukaryotes. However, the roles of kinesins in the atypical cell division of Plasmodium, the causative agent of malaria, is not known. In contrast to many other eukaryotes, Plasmodium proliferates by endomitosis, in which genome replication and division occur within a nucleus bounded by a persistent nuclear envelope. We show that the Plasmodium genome encodes up to nine kinesins and we further investigate the role of kinesin-8X throughout the Plasmodium berghei life cycle using biochemical, cellular and gene targeting approaches. We show that Plasmodium kinesin-8X has microtubule-based motility and depolymerization activity. We also show that kinesin-8X is probably located on putative microtubule organizing centres (MTOCs) and spindles during cell division in most stages of the life cycle. By gene deletion we demonstrate that kinesin-8X is essential for normal oocyst development and sporozoite formation. Genome-wide RNA analysis of Δkinesin-8X gametocytes revealed modulated expression of genes involved in microtubule-based processes. Overall, the data suggest that kinesin-8X is a molecular motor playing an essential role during endomitosis in oocyst development in the mosquito and parasite transmission. |
| Databáze: | OpenAIRE |
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