Apicomplexa Cell Cycles: Something Old, Borrowed, Lost, and New

Abstract

Increased parasite burden is linked to the severity of clinical disease caused by Apicomplexa parasites such as Toxoplasma gondii, Plasmodium spp, and Cryptosporidium. Pathogenesis of apicomplexan infections is greatly affected by the growth rate of the parasite asexual stages. This review discusses recent advances in deciphering the mitotic structures and cell cycle regulatory factors required by Apicomplexa parasites to replicate. As the molecular details become clearer, it is evident that the highly unconventional cell cycles of these parasites is a blending of many ancient and borrowed elements, which were then adapted to enable apicomplexan proliferation in a wide variety of different animal hosts.

Fussing About Fission: Defining Variety Among Mainstream and Exotic Apicomplexan Cell Division Modes

“…In T. gondii it has been demonstrated that the switch from solely a nuclear cycle to a combined nuclear and budding cycle is controlled by a MAP kinase-like protein (Brown et al, 2014;Sugi et al, 2015;Suvorova et al, 2015). Ultimately, cell cycle progression and the activation of each core is regulated by cyclin and CDK pairs adapted to each apicomplexan cycle, as they likely act independently on the innerand outer-centrosome cores (Le Roch et al, 2000;Merckx et al, 2003;Alvarez and Suvorova, 2017;Ganter et al, 2017;Naumov et al, 2017;Robbins et al, 2017;White and Suvorova, 2018). An open question is the identity on the factor(s) controlling the pause of nuclear cycles across parasites prior to the final round of coupled S/M-phase and budding in the polynucleate division modes.…”

“…Specifically, two checkpoints have been described upon commitment to mitosis and budding, one likely dedicated to mitosis and the other to budding. This is thought to facilitate the uncoupling of S/M cycles from budding in the multi-daughter division modes and differentially activate the centrosome inner-and outer-cores (Suvorova et al, 2015;Naumov et al, 2017;White and Suvorova, 2018). Like in schizogony, daughter budding occurs in sync with S/M-phase and karyokinesis.…”

“…means "kinete amplification". kinases (CDKs), as found in higher eukaryotes, ultimately control cell cycle progression but their nature and modes of operation are specifically tailored to the needs of different apicomplexan cell cycle variation (e.g., Roques et al, 2015;Alvarez and Suvorova, 2017;Ganter et al, 2017;Naumov et al, 2017;recently reviewed in Matthews et al, 2018;White and Suvorova, 2018). A second variable is whether karyokinesis follows each S-phase and mitosis (S/M-phase) or not.…”

A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission

“…Interestingly, the C-terminal extensions of both SOC2 and CRK5 are Haemosporidiaspecific. For example, they are absent in the related Apicomplexa parasite Toxoplasma gondii in which the homologue of CRK5 is also involved in DNA replication 13 , highlighting a specific evolution of this cyclin/CDK system in Plasmodium. It is tempting to speculate that the CRK5 C-terminal extension and its phosphorylation are important in the regulation of CRK5 activity by controlling its interaction with SOC2, but this hypothesis remains untested.…”

“…P. berghei Cyc3 is dispensable for blood-stage replication but important for oocyst maturation in the mosquito midgut 11 . The paucity of putative cyclins and the diversity of CDKs, has led to suggestions that some of these kinases function without a cyclin partner 13 .…”