Unambiguous testing of dynamic cytosolic translocation of PDIA1

• Grant number: 20/03193-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: March 01, 2022
• End date: February 28, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Francisco Rafael Martins Laurindo
• Grantee: Percíllia Victória Santos de Oliveira
• Supervisor: Roberto Sitia
• 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
• Institution abroad: 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. (AU)