A novel bipartite centrosome coordinates the apicomplexan cell cycle.

Area of Science:

• Cell Biology
• Parasitology
• Molecular Biology

Background:

• Apicomplexan parasites exhibit remarkable cell cycle flexibility, altering division and proliferation based on host and tissue.
• The centrosome's role in regulating replication timing and scale is crucial but not fully understood.
• Understanding the centrosome's structural and molecular basis is key to deciphering apicomplexan cell cycle control.

Purpose of the Study:

• To discover the structural and molecular basis of cell cycle flexibility in the apicomplexan parasite Toxoplasma gondii.
• To identify and characterize novel protein complexes within the parasite centrosome.
• To elucidate the distinct functions of centrosome sub-structures in regulating parasite proliferation and division.

Main Methods:

• Proteomic analysis to identify protein composition of centrosome core complexes.
• Genetic analysis using temperature-sensitive mutants (ts-TgSfi1) to assess functional roles.
• Microscopy and live-cell imaging to observe centrosome duplication and segregation dynamics.
• Biochemical assays to investigate kinase activity and localization.

Main Results:

• Discovery of a bipartite centrosome organization with distinct outer and inner core complexes.
• Outer core contains TgCentrin1/TgSfi1, TgSas-6, and a novel Aurora-related kinase; inner core contains CEP250/C-Nap orthologs.
• Sequential duplication (outer then inner core) ensures inheritance; a MAPK-related kinase restricts duplication to once per cycle.
• Outer core is essential for cytokinesis, while the inner core co-regulates with the spindle pole (centrocone) for karyokinesis.

Conclusions:

• The novel bipartite centrosome organization segregates karyokinesis and cytokinesis functions in Toxoplasma gondii.
• This structural division provides a molecular explanation for the cell cycle flexibility observed in apicomplexan parasites.
• Targeting these distinct centrosome cores could offer new strategies for controlling parasite proliferation.