SFA2

TgSFA2 is a striated fiber assemblin that organizes cell division in Toxoplasma gondii by physically coupling centrosome duplication to daughter cell budding (PMID:23239939). It polymerizes into a dynamic, polarized fiber that emerges from centrosomes immediately after their duplication and grows toward its distal tip, where daughter cells form and remain tethered at their apical end (conoid and polar ring) (PMID:23239939). Genetic ablation of TgSFA2 blocks cytokinesis at its earliest step — initiation of the daughter microtubule organizing center (MTOC) — while mitosis proceeds unchecked, producing cells with accumulated nuclei but no daughter buds, establishing TgSFA2 as an essential initiator of daughter cell assembly (PMID:23239939). TgSFA2 acts together with TgSFA3 as an essential component of this SFA fiber (PMID:23239939).

1. 2012 High

   It was unknown how centrosome duplication is physically linked to daughter cell formation in Toxoplasma; imaging showed TgSFA2 forms a polarized fiber from newly duplicated centrosomes to which nascent daughters remain apically tethered, establishing a structural connector between the two events.

   Evidence Live imaging and localization in Toxoplasma gondii

   PMID:23239939

   Open questions at the time

   • Molecular mechanism of polarized fiber growth and centrosome nucleation not defined
   • How daughter apical structures physically attach to the fiber tip not resolved
2. 2012 High

   Whether TgSFA2 was required for division and at which step was unknown; loss-of-function arrested cytokinesis at daughter MTOC initiation while permitting mitosis, pinpointing TgSFA2 as an essential trigger of daughter cell budding rather than a mitotic factor.

   Evidence Genetic knockout/conditional knockdown with nuclear-accumulation phenotype in Toxoplasma gondii

   PMID:23239939

   Open questions at the time

   • The signal that couples fiber assembly to MTOC initiation is unknown
   • Interacting partners at the daughter MTOC not identified
3. 2012 Medium

   It was unclear whether TgSFA2 acts alone; epistasis and co-localization showed TgSFA2 and TgSFA3 are both essential components of the same SFA fiber, defining the fiber as a multi-assemblin structure organizing division.

   Evidence Genetic epistasis / double mutant analysis and co-localization in Toxoplasma gondii

   PMID:23239939

   Open questions at the time

   • Stoichiometry and higher-order architecture of the SFA2/SFA3 fiber not determined
   • Single-lab study without independent confirmation

• The biochemical basis of SFA fiber polymerization, its nucleation at the centrosome, and the mechanism by which it triggers daughter MTOC initiation remain uncharacterized in the available corpus.
• No structural model of the SFA fiber
• No defined regulators of fiber assembly/disassembly timing
• Mechanism coupling fiber to MTOC initiation unresolved