Conserved gene microsynteny unveils functional interaction between protein disulfide isomerase and rho guanine-dissociation inhibitor families

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 signa
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.
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Author:Ana Beatriz Silveira Moretti, Jessyca C. Pavanelli, Patrícia Nolasco, Matthias Leisegang, Leonardo Yuji Tanaka, Carolina Gonçalves Fernandes, João Wosniak, Daniela Kajihara, Matheus H. Dias, Denise C. Fernandes, Hanjoong Jo, Ngoc-Vinh Tran, Ingo Ebersberger, Ralf Peter Louis Brandes, Diego Bonatto, Francisco Rafael Martins Laurindo
URN:urn:nbn:de:hebis:30:3-451838
DOI:http://dx.doi.org/10.1038/s41598-017-16947-5
ISSN:2045-2322
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=29222525
Parent Title (English):Scientific reports
Publisher:Macmillan Publishers Limited, part of Springer Nature
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/12/08
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/12/21
Tag:Cell biology; Evolutionary biology
Volume:7
Issue:1, Art. 17262
Pagenumber:18
First Page:1
Last Page:18
Note:
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017
HeBIS PPN:426619714
Institutes:Biowissenschaften
Medizin
Biodiversität und Klima Forschungszentrum (BiK-F)
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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