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Unambiguous testing of dynamic cytosolic translocation of PDIA1

Grant number: 20/03193-8
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): March 01, 2022
Effective date (End): February 28, 2023
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Francisco Rafael Martins Laurindo
Grantee:Percíllia Victória Santos de Oliveira
Supervisor abroad: Roberto Sitia
Home 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
Research place: Università Vita-Salute San Raffaele (UniSR), Italy  
Associated to the scholarship:19/03617-5 - Cytosolic Protein Disulfide Isomerase-A1 (PDIA1): a novel thiol-redox mechanism in cell signaling, BP.PD

Abstract

PDIA1 is an essential, multifunctional enzyme that assists oxidative folding in the ER. It enters cotranslationally into, and resides in, the ER owing to its N-terminal signal sequence and C-terminal KDEL motifs, respectively. Yet, part of PDIA1 is detected extracellularly, where it may control blood clotting and virus entry, and part is found in the cytosol, where it may impact cytoskeletal organization and signaling. Neither the mechanisms that determine the multiple PDIA1 localization, nor their physiological meaning are fully understood. Here we propose to investigate the route(s) followed by PDIA1 to reach the different destinations in living cells. To this end, we will engineer a tagged PDIA1 carrying N-glycans. Biochemical and imaging assays will be used to map its localization, route followed and rate of transport in cells experiencing different stress conditions. In view of the many pathophysiological roles of PDIA1, our results are bound to have relevant basic and translational implications.

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