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The transforming parasite Theileria co-opts host cell mitotic and central spindles to persist in continuously dividing cells

von Schubert, C. and Xue, G. and Schmuckli-Maurer, J. and Woods, K. L. and Nigg, E. A. and Dobbelaere, D. A. E.. (2010) The transforming parasite Theileria co-opts host cell mitotic and central spindles to persist in continuously dividing cells. PLoS Biology, Vol. 8, H. 9 , e1000499.

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Official URL: http://edoc.unibas.ch/dok/A5842434

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Abstract

The protozoan parasite Theileria inhabits the host cell cytoplasm and possesses the unique capacity to transform the cells it infects, inducing continuous proliferation and protection against apoptosis. The transforming schizont is a multinucleated syncytium that resides free in the host cell cytoplasm and is strictly intracellular. To maintain transformation, it is crucial that this syncytium is divided over the two daughter cells at each host cell cytokinesis. This process was dissected using different cell cycle synchronization methods in combination with the targeted application of specific inhibitors. We found that Theileria schizonts associate with newly formed host cell microtubules that emanate from the spindle poles, positioning the parasite at the equatorial region of the mitotic cell where host cell chromosomes assemble during metaphase. During anaphase, the schizont interacts closely with host cell central spindle. As part of this process, the schizont recruits a host cell mitotic kinase, Polo-like kinase 1, and we established that parasite association with host cell central spindles requires Polo-like kinase 1 catalytic activity. Blocking the interaction between the schizont and astral as well as central spindle microtubules prevented parasite segregation between the daughter cells during cytokinesis. Our findings provide a striking example of how an intracellular eukaryotic pathogen that evolved ways to induce the uncontrolled proliferation of the cells it infects usurps the host cell mitotic machinery, including Polo-like kinase 1, one of the pivotal mitotic kinases, to ensure its own persistence and survival.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Nigg, Erich A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
ISSN:1545-7885
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Jun 2012 06:56
Deposited On:08 Jun 2012 06:51

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