SFA3

TgSFA3 is an essential structural component of the striated fiber assemblin (SFA) fiber that organizes cell division in Toxoplasma gondii (PMID:23239939). The SFA fiber, which incorporates TgSFA3 together with TgSFA2, polymerizes from the centrosome immediately after its duplication and grows in a polarized fashion toward the forming daughter cells, physically tethering the daughters at their apical end (conoid and polar ring) and positioning the apical invasion complex during budding (PMID:23239939). Genetic deletion of TgSFA3 blocks cytokinesis at its earliest point—initiation of the daughter microtubule organizing center (MTOC)—while mitosis proceeds unimpeded, causing accumulation of multiple nuclei without daughter cell formation (PMID:23239939). Beyond this role in SFA-fiber-mediated organization of budding, no further mechanistic detail about TgSFA3 has been characterized in the available corpus.

1. 2012 High

   Establishing whether TgSFA3 is required for parasite cell division showed that it is an essential SFA fiber component acting at the earliest step of cytokinesis, defining the fiber as the temporal initiator of daughter formation.

   Evidence Genetic knockout/conditional depletion in Toxoplasma gondii with microscopy phenotyping (cytokinesis block, nuclear accumulation) and live-imaging of fiber dynamics from the centrosome

   PMID:23239939

   Open questions at the time

   • The molecular composition and higher-order structure of the SFA fiber beyond TgSFA3 and TgSFA2 is not resolved
   • How TgSFA3 triggers daughter MTOC initiation mechanistically is not defined
2. 2012 High

   Determining how forming daughters remain spatially linked to the centrosome showed that the SFA fiber grows polarized from the centrosome and tethers daughters at their apical end, establishing the fiber as the spatial organizer positioning the apical invasion complex during budding.

   Evidence Fluorescence microscopy of SFA fiber dynamics during division and genetic epistasis with TgSFA2 and TgSFA3 knockouts in Toxoplasma gondii

   PMID:23239939

   Open questions at the time

   • The mechanism of directional/polarized fiber growth is not defined
   • The interface by which the fiber engages the apical conoid/polar ring is uncharacterized