Identification of mechanisms of protein STI1/Hop secretion

• Grant number: 10/19200-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2011
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Vilma Regina Martins
• Grantee: Marcos Vinicios Salles Dias
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated research grant: 09/14027-2 - Mechanisms associated with the function of prion protein and its ligand STI1/Hop: therapeutic approaches, AP.TEM

Abstract

The co-chaperone STI1 (stress inducible protein 1) or Hop (Hsp70/Hsp90 organizing protein) herein denominated STI1/Hop, was characterized as a prion protein (PrPC) specific ligand. This interaction modulates a number of functions such as protection against apoptosis and neuritogenesis in hippocampal neurons. STI1/Hop is abundantly expressed in cytoplasm but binds PrPC outside of the cell membrane. However, any signal peptide was found within its sequence and mechanisms of STI1/Hop secretion are unknown. Recent data demonstrated that STI1/Hop is secreted in exosome-like vesicles in the conditioned medium of astrocytes and STI1/Hop associated with these lipid vesicles triggers ERK 1/2 signaling pathway in neurons. STI1/Hop secretion is independent of the classical exocytosis pathway through endoplasmatic reticulum/Golgi apparatus. The goal of this project is to identify the routes used by astrocytes to secrete STI1/Hop. We intend to evaluate whether the secretion of STI1/Hop depends on the transport through the endosomal system, incorporation to multivesicular bodies (MVBs) and subsequently secretion by fusion of MVBs with the plasma membrane. The priority of this project is also to evaluate if mechanisms of post-translational modifications or association with specifics membrane domains could be involved in the sorting of STI1/Hop to lipid vesicles. The identification of mechanisms that regulate STI1/Hop secretion will be relevant to understand its neurotrophic properties upon association with PrPC. This complex can be considered a relevant therapeutic target to treat acute lesions in the nervous system as well as in neurodegenerative diseases.

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)

DIAS, MARCOS V. S.; TEIXEIRA, BIANCA L.; RODRIGUES, BRUNA R.; SINIGAGLIA-COIMBRA, RITA; PORTO-CARREIRO, ISABEL; ROFFE, MARTIN; HAJJ, GLAUCIA N. M.; MARTINS, VILMA R.. PRNP/prion protein regulates the secretion of exosomes modulating CAV1/caveolin-1-suppressed autophagy. AUTOPHAGY, v. 12, n. 11, p. 2113-2128, 2016. (12/19019-0, 10/19200-1, 09/14027-2)

SOUSA DE LACERDA, TONIELLI CRISTINA; COSTA-SILVA, BRUNO; GIUDICE, FERNANDA SALGUEIREDO; SALLES DIAS, MARCOS VINICIOS; DE OLIVEIRA, GABRIELA PINTAR; TEIXEIRA, BIANCA LUISE; DOS SANTOS, TIAGO GOSS; MARTINS, VILMA REGINA. Prion protein binding to HOP modulates the migration and invasion of colorectal cancer cells. CLINICAL & EXPERIMENTAL METASTASIS, v. 33, n. 5, p. 441-451, JUN 2016. (12/23285-8, 13/26097-0, 10/19200-1, 09/14027-2, 11/18718-0, 11/20853-2)

BAPTISTEILA, ANTUANI RAFAEL; LANDEMBERGER, MICHELE CHRISTINE; SALLES DIA, MARCOS VINICIOS; GIUDIC, FERNANDA SALGUEIREDO; RODRIGUES, BRUNA ROZ; COMBAS EUFRAZIO DA SILV, PETRUS PAULO; CASSINELA, EDSON KUATELELA; LACERDA, TONIELLI CRISTINA; MARCHI, FABIO ALBUQUERQUE; PAES LEME, ADRIANA FRANCO; et al. Rab5C enhances resistance to ionizing radiation in rectal cancer. JOURNAL OF MOLECULAR MEDICINE-JMM, v. 97, n. 6, p. 855-869, JUN 2019. (10/19200-1, 09/14027-2, 13/04913-0, 11/18718-0)