The exquisite biophysics of the unconventional protein secretion: old and new looks to old and new problems

• Grant number: 23/04532-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: September 01, 2024
• End date: August 31, 2029
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Antonio José da Costa Filho
• Grantee: Antonio José da Costa Filho
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Luis Lamberti Pinto da Silva ; Rosangela Itri
• Associated researchers: Anderson de Sa Pinheiro ; Atílio Tomazini Júnior ; Iasmin Cartaxo Taveira ; Jose Luiz de Souza Lopes ; Lucas Bleicher ; Luis Felipe Santos Mendes ; Maria Cristina Nonato ; Paulo Sergio Rodrigues Coelho
• Associated research grant(s): 24/17969-9 - Multi-user Equipment approved in grant 23/04532-9: Akta Pure 25 L Chromatograph, AP.EMU; 24/17967-6 - Multi-user equipment approved in grant 23/04532-9: refrigerated benchtop centrifuge, AP.EMU
• Associated scholarship(s): 25/10983-9 - "Propensity of GRASPs to undergo liquid-liquid phase separation analyzed through an integrated approach of Monte Carlo simulations and small angle X-ray scattering, BP.PD; 25/11420-8 - Production and testing of lentiviral vectors for expression of GRASP and mutant proteins in human cells, BP.TT; 25/04614-0 - Exploring the biophysics/biochemistry of GRASPs from the causative agent of Chagas' disease and Amoebozoan D. discoideum, BP.DD; 25/02603-1 - Structural Analysis and Anchoring Mechanism of the Transmembrane emp24 domain-containing Proteins, BP.DD

Abstract

The emergence of life diversity and complexity has been facilitated by intercellular communication, which is partially supported by a highly conserved pathway known as the conventional secretory pathway. This pathway involves the secretion of proteins containing a signal peptide through the endoplasmic reticulum-Golgi apparatus-final destination route. Although some questions remain open, its basic machinery has been well-described. Until recently, it was believed that this exocytic route was the sole pathway used by the cell to export a wide range of cargo proteins. However, additional pathways have also been revealed to secrete proteins lacking a signal sequence. These findings challenged the current understanding of a single secretory pathway and have led to exploring alternative routes dedicated to secretion, termed unconventional protein secretion (UPS). Although UPS is becoming increasingly important for cellular adaptation to stress, many crucial aspects of its regulation and biological function are poorly understood. A family of Golgi-resident proteins, the Golgi Reassembly and Stacking Proteins (GRASPs), plays a pivotal role in two of the UPS types described so far. GRASPs are key pillars of this proposal, which irradiates from them to address five different and interconnected aspects of UPS: (1) GRASPs in different organisms; (2) GRASP partners; (3) GRASP and their partner's interactions with membranes; (4) supramolecular arrangments of GRASPs and their partners; (5) in cell studies. This thematic grant proposal intends to bridge the gap between the molecular and cellular worlds by starting from the molecular biophysics of GRASPs and walking along the pathway leading to the cellular implications of what is observed in the test tube. Such a strategy has the potential to yield a better understanding of the fundamental aspects of UPS, with a high impact on cell homeostasis and communication and their disease-related malfunctions. (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)

MAGALHAES, FADI S. S.; VIEIRA, ERNANNI D.; BATISTA, MARIANA R. B.; COSTA-FILHO, ANTONIO J.; BASSO, LUIS G. M.. Effects of Nicotine on the Thermodynamics and Phase Coexistence of Pulmonary Surfactant Model Membranes. MEMBRANES, v. 14, n. 12, p. 25-pg., 2024-12-01. (15/50366-7, 23/04532-9, 15/18390-5)

FREDDI, PRISCILLA; ALVAREZ, NATALIA; FACCHIN, GIANELLA; COSTA-FILHO, ANTONIO J.. Interaction of Phenanthroline-Containing Copper Complexes with Model Phospholipid Membranes. INORGANICS, v. 12, n. 12, p. 12-pg., 2024-12-01. (23/04532-9)