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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, DEC 8 2017.
• Citações Web of Science: 5

Resumo

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)

• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 12/10203-3 - Modularidade gênica das famílias da dissulfeto isomerase proteica e do inibidor da dissociação de guanina: estudos computacionais, moleculares e clonagem da região regulatória
• Beneficiário: Jéssyca Cristine Pavanelli
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• 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
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/24511-7 - Mecanismos e implicações da sinalização via mTORC1 no fenótipo cardiovascular da Síndrome de Marfan
• Beneficiário: Patricia Nolasco Santos
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 15/15281-0 - Caracterização e mecanismos da sinalização parácrina mediada por microRNAs envolvendo mecanoadaptação dependente da dissulfeto isomerase proteica em células vasculares
• Beneficiário: Leonardo Yuji Tanaka
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• 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
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado