Conserved Gene Microsynteny Unveils Functional Interaction Between Protein Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor Families
Abstract 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 mech...
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doaj-ecacaa9b61b844f7b39828427de7b8362020-12-08T02:39:35ZengNature Publishing GroupScientific Reports2045-23222017-12-017111810.1038/s41598-017-16947-5Conserved Gene Microsynteny Unveils Functional Interaction Between Protein Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor FamiliesAna I. S. Moretti0Jessyca C. Pavanelli1Patrícia Nolasco2Matthias S. Leisegang3Leonardo Y. Tanaka4Carolina G. Fernandes5João Wosniak6Daniela Kajihara7Matheus H. Dias8Denise C. Fernandes9Hanjoong Jo10Ngoc-Vinh Tran11Ingo Ebersberger12Ralf P. Brandes13Diego Bonatto14Francisco R. M. Laurindo15Vascular Biology Laboratory, Heart Institute (Incor), University of São Paulo School of MedicineVascular Biology Laboratory, Heart Institute (Incor), University of São Paulo School of MedicineVascular Biology Laboratory, Heart Institute (Incor), University of São Paulo School of MedicineInstitut für Kardiovaskuläre Physiologie, Goethe UniversityVascular Biology Laboratory, Heart Institute (Incor), University of São Paulo School of MedicineVascular Biology Laboratory, Heart Institute (Incor), University of São Paulo School of MedicineVascular Biology Laboratory, Heart Institute (Incor), University of São Paulo School of MedicineVascular Biology Laboratory, Heart Institute (Incor), University of São Paulo School of MedicineSpecial Laboratory for Cell Cycle, Center of Toxins, Immune-Response and Cell Signaling - CeTICS-Cepid, Butantan InstituteVascular Biology Laboratory, Heart Institute (Incor), University of São Paulo School of MedicineThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityApplied Bioinformatics Group, Institute of Cell Biology & Neuroscience, Goethe UniversityApplied Bioinformatics Group, Institute of Cell Biology & Neuroscience, Goethe UniversityInstitut für Kardiovaskuläre Physiologie, Goethe UniversityDepartment of Molecular Biology and Biotechnology, Federal University of Rio Grande do SulVascular Biology Laboratory, Heart Institute (Incor), University of São Paulo School of MedicineAbstract 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/RhoGDIα 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.https://doi.org/10.1038/s41598-017-16947-5 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ana I. S. Moretti Jessyca C. Pavanelli Patrícia Nolasco Matthias S. Leisegang Leonardo Y. Tanaka Carolina G. Fernandes João Wosniak Daniela Kajihara Matheus H. Dias Denise C. Fernandes Hanjoong Jo Ngoc-Vinh Tran Ingo Ebersberger Ralf P. Brandes Diego Bonatto Francisco R. M. Laurindo |
spellingShingle |
Ana I. S. Moretti Jessyca C. Pavanelli Patrícia Nolasco Matthias S. Leisegang Leonardo Y. Tanaka Carolina G. Fernandes João Wosniak Daniela Kajihara Matheus H. Dias Denise C. Fernandes Hanjoong Jo Ngoc-Vinh Tran Ingo Ebersberger Ralf P. Brandes Diego Bonatto Francisco R. M. Laurindo Conserved Gene Microsynteny Unveils Functional Interaction Between Protein Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor Families Scientific Reports |
author_facet |
Ana I. S. Moretti Jessyca C. Pavanelli Patrícia Nolasco Matthias S. Leisegang Leonardo Y. Tanaka Carolina G. Fernandes João Wosniak Daniela Kajihara Matheus H. Dias Denise C. Fernandes Hanjoong Jo Ngoc-Vinh Tran Ingo Ebersberger Ralf P. Brandes Diego Bonatto Francisco R. M. Laurindo |
author_sort |
Ana I. S. Moretti |
title |
Conserved Gene Microsynteny Unveils Functional Interaction Between Protein Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor Families |
title_short |
Conserved Gene Microsynteny Unveils Functional Interaction Between Protein Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor Families |
title_full |
Conserved Gene Microsynteny Unveils Functional Interaction Between Protein Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor Families |
title_fullStr |
Conserved Gene Microsynteny Unveils Functional Interaction Between Protein Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor Families |
title_full_unstemmed |
Conserved Gene Microsynteny Unveils Functional Interaction Between Protein Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor Families |
title_sort |
conserved gene microsynteny unveils functional interaction between protein disulfide isomerase and rho guanine-dissociation inhibitor families |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-12-01 |
description |
Abstract 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/RhoGDIα 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. |
url |
https://doi.org/10.1038/s41598-017-16947-5 |
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