Apicomplexan cell cycle flexibility: centrosome controls the clutch

Abstract

The centrosome serves as a central hub coordinating multiple cellular events in eukaryotes. A recent study in Toxoplasma gondii revealed a unique bipartite structure of the centrosome, which coordinates the nuclear cycle (S-phase and mitosis) and budding cycle (cytokinesis) of the parasite, and deciphers the principle behind flexible apicomplexan cell division modes.

TgCep250 is dynamically processed through the division cycle and essential for structural integrity of the Toxoplasma centrosome

“…These results indicate that the function of the outer-core in daughter bud assembly remains intact when it is detached from the inner-core. This observation is in line with the proposed working model predicting that the inner-core and outer-core functions can act independently 7, 19 .…”

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

“…The inner core is copied after the outer core in S phase ( Figure 2 ), and contains orthologs of the coiled-coiled centrosomal proteins of higher eukaryotes, while lacking centrin [ 13 , 27 ]. Functionally, the inner core is required for chromosome replication in the tachyzoite [ 13 , 28 ], and in genetic mutants that over-duplicate the inner core the centrocone is also over duplicated [ 13 ]. These results indicate that the inner core and centrocone constitute a complete spindle pole complex in these parasites.…”

“…To provide differential control of periodic and constitutive synthesis, the eukaryotic cell cycle alternates between growth and DNA replication/segregation phases, always obeying the rule that cell size dictates the time and scale of replication [ 52 , 57 ], Apicomplexans appear to follow this old rule where the number of chromosome duplications (nuclear cycles) [ 13 , 28 ], and ultimately the scale of progeny production, are predetermined by the time parasites spend in the G1 growth phase. For example, T. gondii tachyzoites and P. falciparum merozoites produce 2 versus 32 progeny, respectively, after G1 phases of ~3 versus 12 h. At the extreme end of Apicomplexa replication, is the ~6 day G1 phase of the Eimeria bovis sporozoite that produces thousands of daughter parasites.…”

A checkpoint roadmap for the complex cell division of Apicomplexa parasites

“…ATc-downregulation of TgCrk6 disrupted the usual dynamics of kinetochores visualized by co-staining of the kinetochore complex component, TgNdc80 myc , and acetylated Tubulin A that labels active sites of the microtubule assembly including spindle and internal daughters ( Fig 6B) [24]. In normal parasites, the TgNdc80 myc signal largely disappeared at mid-bud development ( apicomplexans) that coordinates attachment of nuclear centromeres to kinetochores/spindle and to a unique centrosome containing two independent functioning core structures [3,22]. Consistent with a role in controlling mitosis through cytoplasmic structures, down regulation of TgCrk4 with 1µg/ml ATc led to defective duplication of both centrosomal cores (Centrin1/outer core and CEP250 myc /inner core), but did not affect centromere duplication/segregation (CenH3 marker) or nuclear division ( Fig 7A).…”

“…During the apicomplexan mitosis numerous specialized structures are replicated, built or converted in precise order to produce healthy infectious daughters (for review see [2,22]). Our previous work and the studies of others have established that duplication of the bipartite centrosome is coordinated with division of the centrocone that holds the mitotic spindle [3,6,10,23], and also with the replication and segregation of the bundled centromeres [23,24], which in turn, is synchronized with assembly of the basal and apical complexes of the future daughter [25][26][27][28].…”