Exploring the dynamic assembly/disassembly of a Golgi matrix protein under stress-conditions

• Grant number: 21/10465-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2022
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Antonio José da Costa Filho
• Grantee: Luis Felipe Santos Mendes
• Supervisor: Roland Riek
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Swiss Federal Institute of Technology Zurich, Switzerland
• Associated to the scholarship: 17/24669-8 - Unraveling the molecular bases of the early protein secretory pathway in humans using biophysical techniques, BP.PD

Abstract

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. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FREIRE, MARJORIE C. L. C.; BASSO, LUIS G. M.; MENDES, LUIS F. S.; MESQUITA, NATHALYA C. M. R.; MOTTIN, MELINA; FERNANDES, RAFAELA S.; POLICASTRO, LUCCA R.; GODOY, ANDRE S.; SANTOS, IGOR A.; RUIZ, URIEL E. A.; et al. Characterization of the RNA-dependent RNA polymerase from Chikungunya virus and discovery of a novel ligand as a potential drug candidate. SCIENTIFIC REPORTS, v. 12, n. 1, p. 15-pg., 2022-06-22. (18/17095-8, 18/05130-3, 15/16812-0, 21/10465-7, 13/07600-3, 17/24669-8, 21/01706-0)

MENDES, LUIS FELIPE S.; COSTA-FILHO, ANTONIO J.. A gold revision of the Golgi Dynamics (GOLD) domain structure and associated cell functionalities. FEBS Letters, v. 596, n. 8, p. 18-pg., 2022-02-14. (17/24669-8, 20/15542-7, 15/50366-7, 21/10465-7)