title: The cell cycle and Toxoplasma gondii cell division: tightly knit or loosely stitched?
abstract: The flexibility displayed by apicomplexan parasites to vary their mode of replication has intrigued biologists since their discovery by electron microscopy in the 1960s and 1970s. Starting in the 1990s we began to understand the cell biology of the cytoskeleton elements driving cytokinesis. By contrast, the molecular mechanisms that regulate the various division modes and how they translate into the budding process that uniquely characterizes this parasite family are much less understood. Although growth mechanisms are a neglected area of study, it is an important pathogenic parameter as fast division rounds are associated with fulminant infection whereas slower growth attenuates virulence, as is exploited in some vaccine strains. In this review we summarize a recent body of cell biological experiments that are rapidly leading to an understanding of the events that yield successful mitosis and cytokinesis in Toxoplasma. We place these observations within a cell cycle context with comments on how these events may be regulated by known eukaryotic checkpoints active in fission and budding yeasts as well as mammalian cells. The presence of cell cycle control mechanisms in the Apicomplexa is supported by our findings that identify several cell cycle checkpoints in Toxoplasma. The progress of the cell cycle is ultimately controlled by cyclin-Cdk pair activities, which are present throughout the Apicomplexa. Although many of the known controllers of cyclin-Cdk activity are present, several key controls cannot readily be identified, suggesting that apicomplexan parasites deviate at these points from the higher eukaryotic models. Altogether, new insights in Toxoplasma replication are reciprocally applied to hypothesize how other division modes in the Toxoplasma life cycle and in other Apicomplexa species could be controlled in terms of cell cycle checkpoint regulation.
authors.affiliation: Department of Biology, Boston College, 355 Higgins Hall, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. gubbelsj@bc.edu
authors.forename: Marc-Jan
authors.initials: MJ
authors.lastname: Gubbels
authors.forename: Michael
authors.initials: M
authors.lastname: White
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szatanek
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology; D008938:Mitosis / Q000502:physiology; D014122:Toxoplasma / Q000166:cytology*; D014123:Toxoplasmosis / Q000517:prevention & control
chemical_list: D016213:Cyclins