Eukaryotic cells have a complex and regulated secretory system that can deal with up to 30% of the total proteome. A subfamily of the Golgi matrix proteins called Golgi Reassembly and Stacking Proteins (GRASP), which are critical players in the unconventional, stress-induced, secretory pathway (UPS), was also shown to be fundamental for the Golgi dynamics during mitosis/apoptosis and Golgi ribbon formation. GRASPs have an in vitro tendency of forming a condensed phase with a solid-like character under stress conditions, known as the amyloid-state. The GRASP amyloid formation tendency was also observed in vivo in conditions that trigger UPS and heat shock response (HSR). Therefore, GRASP structural plasticity and its ability to form complex arrangements seem to be a new piece of information that needs to be accounted for when describing their many cell roles. The condensate formation needs to be fully reversible for the cells to return to their native conditions after the stress conditions are removed. However, the mechanism of GRASP fibres dissociation remains elusive. Since proteins in physiological conditions are near the supersaturation limits at their typical cellular concentrations, GRASP condensates might also play an important role in Golgi organization under native conditions, a hypothesis still unexplored. This proposal intends to explore the dynamic of GRASP aggregation/disaggregation under stress-relevant conditions and their morphology variations using high-resolution techniques. GRASP fibres association with the membranes will also be explored to map GRASP involvement in cell stress and normal conditions.
News published in Agência FAPESP Newsletter about the scholarship: