Unraveling the molecular bases of the early protein secretory pathway in humans using biophysical techniques

• Grant number: 17/24669-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2018
• End date: February 28, 2023
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Antonio José da Costa Filho
• Grantee: Luis Felipe Santos Mendes
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID
• Associated scholarship(s): 21/10465-7 - Exploring the dynamic assembly/disassembly of a Golgi matrix protein under stress-conditions, BE.EP.PD

Abstract

Each and every living cell evolved in a way where an efficient biomolecular secretion system was created in order to attend its basal biological needs and the way they interact with external systems. In this sense, eukaryotic cells enormously differ from prokaryote ones, possessing an extensive biomembrane system in their intracellular part, where different compartments with specific functions are present and require constant exchanges of molecules with each other. Proteins whose final destination is either the extracellular medium or the plasma membrane are initially synthesized within the endoplasmic reticulum (ER) and then addressed to the Golgi complex, where they are packaged and transported to their final destination. Although it has been a subject of intense studies since its discovery, this (classical) pathway of secretion still has several points that need elucidation, especially those related to how proteins are selected in the ER, transported to the Golgi and to how the latter organelle efficiently captures and retains a transport cargo. A family of membrane proteins known as p24 is suggested as the key factor in the process of capturing non-ER proteins and their targeting to the Golgi, as well as an involvement in the Golgi retention process, where it would act together with another protein known as Golgi Reassembly and Stacking Protein (GRASP). With this proposal, we intend to provide key information on the mechanism of action of p24 in humans, its retention process in the Golgi and their involvement in membrane expression of protein receptors with roles in pro-inflammatory responses. (AU)

Scientific publications

(11)

(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)

ALVAREZ, NATALIA; MENDES, LUIS F. S.; GABRIELA KRAMER, M.; TORRE, MARIA H.; COSTA-FILHO, ANTONIO J.; ELLENA, JAVIER; FACCHIN, GIANELLA. Development of copper(II)-diimine-iminodiacetate mixed ligand complexes as potential antitumor agents. Inorganica Chimica Acta, v. 483, p. 61-70, NOV 1 2018. (12/13309-7, 17/24669-8)

MENDES, LUIS F. S.; FONTANA, NATALIA A.; OLIVEIRA, CAROLINA G.; FREIRE, MARJORIE C. L. C.; LOPES, JOSE L. S.; MELO, FERNANDO A.; COSTA-FILHO, ANTONIO J.. The GRASP domain in golgi reassembly and stacking proteins: differences and similarities between lower and higher Eukaryotes. FEBS Journal, v. 286, n. 17, p. 3340-3358, SEP 2019. (17/24669-8, 12/20367-3, 15/50366-7, 09/53989-4, 16/23863-2)

MENDES, LUIS FELIPE S.; BATISTA, MARIANA R. B.; JUDGE, PETER J.; WATTS, ANTHONY; REDFIELD, CHRISTINA; COSTA-FILHO, ANTONIO J.. Conformational flexibility of GRASPs and their constituent PDZ subdomains reveals structural basis of their promiscuous interactome. FEBS Journal, v. 287, n. 15, JAN 2020. (12/20367-3, 15/50366-7, 16/09676-5, 17/24669-8)

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)

KAVA, EMANUEL; MENDES, LUIS F. S.; BATISTA, MARIANA R. B.; COSTA-FILHO, ANTONIO J.. Myristoylation and its effects on the human Golgi Reassembly and Stacking Protein 55. Biophysical Chemistry, v. 279, DEC 2021. (15/50366-7, 16/16328-3, 17/24669-8, 12/20367-3)

MENDES, LUIS F. S.; FONTANA, NATALIA A.; REDDY, S. THIRUPATHI; UVERSKY, VLADIMIR N.; COSTA-FILHO, ANTONIO J.. The exquisite structural biophysics of the Golgi Reassembly and Stacking Proteins. International Journal of Biological Macromolecules, v. 164, p. 3632-3644, DEC 1 2020. (12/20367-3, 15/50366-7, 16/23863-2, 17/24669-8, 17/12146-0)

MENDES, LUIS F. S.; BATISTA, MARIANA R. B.; KAVA, EMANUEL; BLEICHER, LUCAS; MICHELETTO, MARIANA C.; COSTA-FILHO, ANTONIO J.. Resurrecting Golgi proteins to grasp Golgi ribbon formation and self-association under stress. International Journal of Biological Macromolecules, v. 194, p. 264-275, JAN 1 2022. (16/16328-3, 15/16812-0, 15/50366-7, 12/20367-3, 18/13016-6, 17/24669-8)

ALVAREZ, NATALIA; VINA, DIANA; LEITE, CELISNOLIA M.; MENDES, LUIS F. S.; BATISTA, ALZIR A.; ELLENA, JAVIER; COSTA-FILHO, ANTONIO J.; FACCHIN, GIANELLA. Synthesis and structural characterization of a series of ternary copper(II)-L-dipeptide-neocuproine complexes. Study of their cytotoxicity against cancer cells including MDA-MB-231, triple negative breast cancer cells. Journal of Inorganic Biochemistry, v. 203, FEB 2020. (15/50366-7, 17/24669-8)

THIRUPATHI REDDY, S.; SANTOS MENDES, LUIS FELIPE; FONTANA, NATALIA APARECIDA; COSTA-FILHO, ANTONIO JOSE. Exploring structural aspects of the human Golgi matrix protein GRASP55 in solution. International Journal of Biological Macromolecules, v. 135, p. 481-489, AUG 15 2019. (16/23863-2, 17/12146-0, 17/24669-8, 15/16812-0, 15/50366-7, 12/20367-3)

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)

MOTA, DANIELLY C. A. M.; CARDOSO, IARA A.; MORI, RENAN M.; BATISTA, MARIANA R. B.; BASSO, LUIS G. M.; NONATO, M. CRISTINA; COSTA-FILHO, ANTONIO J.; MENDES, LUIS F. S.. Structural and thermodynamic analyses of human TMED1 (p24 gamma 1) Golgi dynamics. Biochimie, v. 192, p. 11-pg., 2022-01-01. (15/16812-0, 17/24669-8, 15/50366-7)