Molecular dissection of cell division in apicomplexan parasites
Francia, Maria Eugenia
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Apicomplexa are intracellular parasites that cause important human diseases including malaria and toxoplasmosis. Following invasion of a host cell, Apicomplexa undergo a fascinatingly complex process of division. Apicomplexa proliferate by a unique mechanism that combines closed mitosis of the nucleus with de-novo formation of daughter cells. Mitosis occurs in the presence of a nuclear envelope and with little appreciable chromatin condensation. Nuclear division is not always followed by cytokinesis. In some Apicomplexa, division results in a cytosol in which multiple nuclei and organelles are parceled into multiple daughter cells simultaneously. Budding is remarkably flexible in output and can produce two to thousands of progeny cells depending on the apicomplexan species. How genomes and daughters are counted and coordinated is unknown. Here, we use Toxoplasma gondii as a cell biological model to ask questions pertaining molecular aspects of apicomplexan division. We had shown previously that all centromeres, the sites of kinetochore attachment on each chromosome, are constantly tethered to the centrosome positioned in a specific region of the nuclear periphery. Centromeres are clustered throughout the cell cycle. We show that centromere clustering is mediated by elements of the nuclear envelope. In particular, components of the nuclear pore complex appear to be important for maintenance of centromere tethered to the nuclear envelope. We also show that nuclear events are coordinated with assembly of daughter cells through structures associated to the centrosome during division. A fiber-like structure, derived from the algal past of apicomplexan parasites, assembles on the centrosome during mitosis and initiates daughter cell assembly. This fiber is made of striated fiber assemblin proteins which in algae participate in the positioning and organization of the flagellar basal body. These findings have broad evolutionary implications. We propose that Apicomplexa retained the organizing principle of the flagellar microtubule organizing center. Instead of ensuring appropriate numbers of flagella, the system now positions the microtubule organizing center of the daughter cell. Finally, the results herein presented derive a novel model of regulation of division in which individual elements of the cell are linked through physical tethers to the centrosome providing both spatial organization and temporal control.