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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Conserved Gene Microsynteny Unveils Functional Interaction Between Protein Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor Families

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Moretti, Ana I. S. [1] ; Pavanelli, Jessyca C. [1] ; Nolasco, Patricia [1] ; Leisegang, Matthias S. [2] ; Tanaka, Leonardo Y. [1] ; Fernandes, Carolina G. [1] ; Wosniak, Jr., Joao [1] ; Kajihara, Daniela [1] ; Dias, Matheus H. [3] ; Fernandes, Denise C. [1] ; Jo, Hanjoong [4, 5] ; Tran, Ngoc-Vinh ; Ebersberger, Ingo [6, 7] ; Brandes, Ralf P. [2] ; Bonatto, Diego [8] ; Laurindo, Francisco R. M. [1]
Total Authors: 16
[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Vasc Biol Lab, Sao Paulo - Brazil
[2] Goethe Univ, Inst Kardiovaskulare Physiol, Frankfurt - Germany
[3] Butantan Inst, Ctr Toxins Immune Response & Cell Signaling CeTIC, Special Lab Cell Cycle, Sao Paulo - Brazil
[4] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 - USA
[5] Emory Univ, Atlanta, GA 30322 - USA
[6] Ngoc-Vinh Tran, Goethe Univ, Inst Cell Biol Neurosci, Appl Bioinformat Grp, Frankfurt - Germany
[7] Senckenberg Biodivers & Climate Res Ctr BiK F, Frankfurt - Germany
[8] Univ Fed Rio Grande do Sul, Dept Mol Biol & Biotechnol, Porto Alegre, RS - Brazil
Total Affiliations: 8
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 7, DEC 8 2017.
Web of Science Citations: 5

Protein disulfide isomerases (PDIs) support endoplasmic reticulum redox protein folding and cell-surface thiol-redox control of thrombosis and vascular remodeling. The family prototype PDIA1 regulates NADPH oxidase signaling and cytoskeleton organization, however the related underlying mechanisms are unclear. Here we show that genes encoding human PDIA1 and its two paralogs PDIA8 and PDIA2 are each flanked by genes encoding Rho guanine-dissociation inhibitors (GDI), known regulators of RhoGTPases/cytoskeleton. Evolutionary histories of these three microsyntenic regions reveal their emergence by two successive duplication events of a primordial gene pair in the last common vertebrate ancestor. The arrangement, however, is substantially older, detectable in echinoderms, nematodes, and cnidarians. Thus, PDI/RhoGDI pairing in the same transcription orientation emerged early in animal evolution and has been largely maintained. PDI/RhoGDI pairs are embedded into conserved genomic regions displaying common cis-regulatory elements. Analysis of gene expression datasets supports evidence for PDI/RhoGDI coexpression in developmental/inflammatory contexts. PDIA1/RhoGDIa were co-induced in endothelial cells upon CRISP-R-promoted transcription activation of each pair component, and also in mouse arterial intima during flow-induced remodeling. We provide evidence for physical interaction between both proteins. These data support strong functional links between PDI and RhoGDI families, which likely maintained PDI/RhoGDI microsynteny along > 800-million years of evolution. (AU)

FAPESP's process: 14/24511-7 - Mechanisms and implications of the mTORC1 signaling pathway in the cardiovascular phenotype of Marfan Syndrome
Grantee:Patricia Nolasco Santos
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 12/10203-3 - Genetic modularity of protein disulfide isomerase and guanine dissociation inhibitor families: computational and molecular studies and cloning of the regulatory region
Grantee:Jéssyca Cristine Pavanelli
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 09/54764-6 - Regulation of redox homeostasis and integrated stress response by Protein Disulfide Isomerase (PDI): mechanisms and role in the pathophysiology and therapy of vascular diseases
Grantee:Francisco Rafael Martins Laurindo
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 15/15281-0 - Characterization and mechanisms of microRNA-mediated paracrine signaling involving protein disulfide isomerase-dependent mechano-adaptation in vascular cells
Grantee:Leonardo Yuji Tanaka
Support type: Scholarships abroad - Research Internship - Post-doctor