Advanced search
Start date

Cytosolic Protein Disulfide Isomerase-A1 (PDIA1): a novel thiol-redox mechanism in cell signaling

Grant number: 19/03617-5
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2019
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Francisco Rafael Martins Laurindo
Grantee:Percíllia Victória Santos de Oliveira
Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID
Associated scholarship(s):20/03193-8 - Unambiguous testing of dynamic cytosolic translocation of PDIA1, BE.EP.PD


Protein disulfide isomerase-A1 (PDIA1) is a dithiol-disulfide oxidoreductase chaperone with a major canonical function of redox protein folding (disulfide bond formation/isomerization) in nascent proteins at the endoplasmic reticulum (ER). Thus, PDIA1 exerts a central role in ER-associated proteostasis and redox balance. The quantitatively smaller PDIA1 pool at the cell surface and extracellular milieu (pecPDIA1) has been extensively studied in distinct processes including thiol-redox modulation of thrombosis, vascular remodeling and mechanoadaptation. Our group has described physiological effects of PDIA1 associated with redox signaling pathways, e.g., convergence with NADPH oxidases and interaction with cytoskeleton and cytosolic proteins. In this context, we have consolidated a new concept, namely the existence of a cytoplasmic PDIA1 pool associated with specific effects on redox-regulated cytoskeletal proteins and mechanosignaling. However, the possible cytoplasmic location of PDIA1, as well as other thiol isomerases, remains controversial. The general question of this project is based on the hypothesis that there is a consistent cytosolic-located PDIA1 fraction which can potentially interact, in a thiol redox mannerway, with substrates related to cytoskeletal organization and cellular architecture. The specific aims are: 1) To characterize in detail the PDIA1 location and its redox state in the cytosolic fraction; 2) To investigate the potential routes by which PDIA1 reach extracellular space or cytosol; 3) To investigate possible cytosolic PDIA1 substrates modulated by thiol-redox activities. Aim 2 involves an already programmed BEPE project. These results may have important implications to sediment a new concept: the role of intracellular PDIA1 as an adaptor/organizer protein exerting localized and substrate-specific regulatory processes, not yet described, regarding redox modulation of cytoskeleton-related protein targets. These data may also generate relevant advances for understanding the cytosolic redox network, as well new investigative tools and potential therapeutic targets related to novel interactions.

News published in Agência FAPESP Newsletter about the scholarship:
Articles published in other media outlets (0 total):
More itemsLess items

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)
TANAKA, LEONARDO Y.; OLIVEIRA, PERCILLIA V. S.; LAURINDO, FRANCISCO R. M.. Peri/Epicellular Thiol Oxidoreductases as Mediators of Extracellular Redox Signaling. Antioxidants & Redox Signaling, v. 33, n. 4, . (18/07230-5, 13/07937-8, 19/03617-5)

Please report errors in scientific publications list by writing to: