Protein disulfide isomerases: Redox connections in and out of the endoplasmic reticulum

Autor(es)

Soares Moretti, Ana Iochabel ; Martins Laurindo, Francisco Rafael

• Tipo de documento: Artigo Científico
• Fonte: Archives of Biochemistry and Biophysics; v. 617, p. 14-pg., 2017-03-01.

Resumo

Protein disulfide isomerases are thiol oxidoreductase chaperones from thioredoxin superfamily. As redox folding catalysts from the endoplasmic reticulum (ER), their roles in ER-related redox homeostasis and signaling are well-studied. PDIA1 exerts thiol oxidation/reduction and isomerization, plus chaperone effects. Also, substantial evidence indicates that PDIs regulate thiol-disulfide switches in other cell locations such as cell surface and possibly cytosol. Subcellular PDI translocation routes remain unclear and seem Golgi-independent. The list of signaling and structural proteins reportedly regulated by PDIs keeps growing, via thiol switches involving oxidation, reduction and isomerization, S-(de)nytrosylation, (de) glutathyonylation and protein oligomerization. PDIA1 is required for agonist-triggered Nox NADPH oxidase activation and cell migration in vascular cells and macrophages, while PDIA1-dependent cytoskeletal regulation appears a converging pathway. Extracellularly, PDIs crucially regulate thiol redox signaling of thrombosis/platelet activation, e.g., integrins, and PDIA1 supports expansive caliber remodeling during injury repair via matrix/cytoskeletal organization. Some proteins display regulatory PDI-like motifs. PDI effects are orchestrated by expression levels or post-translational modifications. PDI is redox-sensitive, although probably not a mass-effect redox sensor due to kinetic constraints. Rather, the "all-in-one" organization of its peculiar redox/chaperone properties likely provide PDIs with precision and versatility in redox signaling, making them promising therapeutic targets. (C) 2016 Published by Elsevier Inc. (AU)

• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 09/54764-6 - Regulação da homeostase redox e resposta integrada a estresse pela dissulfeto isomerase protéica (PDI): mecanismos e papel na fisiopatologia e terapêutica de doenças vasculares
• Beneficiário: Francisco Rafael Martins Laurindo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/50469-0 - Interacao entre dissulfeto isomera interacao entre dissulfeto isomerase proteica, rhogdie gtpases da familia rho e ras:identificacao de complexos proteicos.
• Beneficiário: Ana Iochabel Soares Moretti
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/23657-8 - Estudo funcional da interação entre a proteína disulfeto isomerase (PDI) e a proteína ligante de actina, Profilina 1
• Beneficiário: Ana Iochabel Soares Moretti
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado