Figure 8: Model of TGIF function in microneme and rhoptry trafficking.

Working model of the secretory pathway in T. gondii. After ER synthesis, MIC2 and RON2 traffic through the Golgi to the Post-Golgi compartments which comprise the PLVAC and Rab5a ELC (purple) and transport vesicles. Proteins are then found in micronemes (dark blue) and in the rhoptry neck (yellow). After synthesis ROP1 (green) rapidly exists the ER. We propose two potential models for ROP1 trafficking. In model 1, ROP1 uses a Golgi bypass pathway in wildtype parasites. ROP1 vesicles are trafficked from the ER either directly to the apical end or through the post-Golgi compartment(s). We propose that mature rhoptry bulbs form from fusion vesicles containing rhoptry bulb and rhoptry neck proteins. Alternatively, in model 2, ROP1 traffics through the cis- and trans- Golgi and then to the post-Golgi compartment before trafficking in vesicles to the apical end for maturation in wildtype parasites. When TGIF is depleted, ROP1 exit from the ER is not disrupted indicating it traffics via a Golgi-independent pathway. Once at the apical end, bulb formation is perturbed, suggesting the trafficking of factors necessary for bulb maturation is disrupted. Loss of TGIF also results in decreased synthesis of MIC2 and RON2 and accumulation of newly synthesized proteins in post-Golgi compartments or adjacent vesicles. Expanded ER lumen and disorganized cis-cisternae are observed in the absence of TGIF. Arrows indicate trafficking pathways; ROP1 in green, MIC2 in blue, RON2 in yellow. Dashed arrow indicates decreased trafficking. Blunt arrow indicates blocked trafficking pathways.