Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions
Guanylate binding proteins (GBPs) are an evolutionarily ancient family of proteins that are widely distributed among eukaryotes. They belong to the dynamin superfamily of GTPases, and their expression can be partially induced by interferons (IFNs). GBPs are involved in the cell-autonomous innate imm...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1303089/full |
| _version_ | 1797341252195188736 |
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| author | Luca Schelle João Vasco Côrte-Real João Vasco Côrte-Real João Vasco Côrte-Real João Vasco Côrte-Real Sharmeen Fayyaz Sharmeen Fayyaz Augusto del Pozo Ben Margarita Shnipova Moritz Petersen Rishikesh Lotke Bhavna Menon Dana Matzek Lena Pfaff Ana Pinheiro Ana Pinheiro João Pedro Marques João Pedro Marques João Pedro Marques José Melo-Ferreira José Melo-Ferreira José Melo-Ferreira Bastian Popper Pedro José Esteves Pedro José Esteves Pedro José Esteves Pedro José Esteves Daniel Sauter Joana Abrantes Joana Abrantes Joana Abrantes Hanna-Mari Baldauf |
| author_facet | Luca Schelle João Vasco Côrte-Real João Vasco Côrte-Real João Vasco Côrte-Real João Vasco Côrte-Real Sharmeen Fayyaz Sharmeen Fayyaz Augusto del Pozo Ben Margarita Shnipova Moritz Petersen Rishikesh Lotke Bhavna Menon Dana Matzek Lena Pfaff Ana Pinheiro Ana Pinheiro João Pedro Marques João Pedro Marques João Pedro Marques José Melo-Ferreira José Melo-Ferreira José Melo-Ferreira Bastian Popper Pedro José Esteves Pedro José Esteves Pedro José Esteves Pedro José Esteves Daniel Sauter Joana Abrantes Joana Abrantes Joana Abrantes Hanna-Mari Baldauf |
| author_sort | Luca Schelle |
| collection | DOAJ |
| description | Guanylate binding proteins (GBPs) are an evolutionarily ancient family of proteins that are widely distributed among eukaryotes. They belong to the dynamin superfamily of GTPases, and their expression can be partially induced by interferons (IFNs). GBPs are involved in the cell-autonomous innate immune response against bacterial, parasitic and viral infections. Evolutionary studies have shown that GBPs exhibit a pattern of gene gain and loss events, indicative for the birth-and-death model of evolution. Most species harbor large GBP gene clusters that encode multiple paralogs. Previous functional and in-depth evolutionary studies have mainly focused on murine and human GBPs. Since rabbits are another important model system for studying human diseases, we focus here on lagomorphs to broaden our understanding of the multifunctional GBP protein family by conducting evolutionary analyses and performing a molecular and functional characterization of rabbit GBPs. We observed that lagomorphs lack GBP3, 6 and 7. Furthermore, Leporidae experienced a loss of GBP2, a unique duplication of GBP5 and a massive expansion of GBP4. Gene expression analysis by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and transcriptome data revealed that leporid GBP expression varied across tissues. Overexpressed rabbit GBPs localized either uniformly and/or discretely to the cytoplasm and/or to the nucleus. Oryctolagus cuniculus (oc)GBP5L1 and rarely ocGBP5L2 were an exception, colocalizing with the trans-Golgi network (TGN). In addition, four ocGBPs were IFN-inducible and only ocGBP5L2 inhibited furin activity. In conclusion, from an evolutionary perspective, lagomorph GBPs experienced multiple gain and loss events, and the molecular and functional characteristics of ocGBP suggest a role in innate immunity. |
| first_indexed | 2024-03-08T10:15:13Z |
| format | Article |
| id | doaj.art-f9eaed9ec78849db87f66e1c42b9f5e4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T10:15:13Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f9eaed9ec78849db87f66e1c42b9f5e42024-01-29T04:20:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011510.3389/fimmu.2024.13030891303089Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functionsLuca Schelle0João Vasco Côrte-Real1João Vasco Côrte-Real2João Vasco Côrte-Real3João Vasco Côrte-Real4Sharmeen Fayyaz5Sharmeen Fayyaz6Augusto del Pozo Ben7Margarita Shnipova8Moritz Petersen9Rishikesh Lotke10Bhavna Menon11Dana Matzek12Lena Pfaff13Ana Pinheiro14Ana Pinheiro15João Pedro Marques16João Pedro Marques17João Pedro Marques18José Melo-Ferreira19José Melo-Ferreira20José Melo-Ferreira21Bastian Popper22Pedro José Esteves23Pedro José Esteves24Pedro José Esteves25Pedro José Esteves26Daniel Sauter27Joana Abrantes28Joana Abrantes29Joana Abrantes30Hanna-Mari Baldauf31Max von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, GermanyMax von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, GermanyCIBIO-InBIO, Research Center in Biodiversity and Genetic Resources, University of Porto, Vairão, PortugalDepartment of Biology, Faculty of Sciences, University of Porto, Porto, PortugalBIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, Vairão, PortugalInstitute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, GermanyNational Institute of Virology, International Center of Chemical and Biological Sciences, University of Karachi, Karachi, PakistanMax von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, GermanyMax von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, GermanyInstitute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, GermanyInstitute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, GermanyMax von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, GermanyBiomedical Center (BMC), Core facility Animal Models (CAM), Faculty of Medicine, LMU München, Munich, GermanyBiomedical Center (BMC), Core facility Animal Models (CAM), Faculty of Medicine, LMU München, Munich, GermanyCIBIO-InBIO, Research Center in Biodiversity and Genetic Resources, University of Porto, Vairão, PortugalBIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, Vairão, PortugalCIBIO-InBIO, Research Center in Biodiversity and Genetic Resources, University of Porto, Vairão, PortugalBIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, Vairão, PortugalISEM, University of Montpellier, CNRS, EPHE, IRD, Montpellier, FranceCIBIO-InBIO, Research Center in Biodiversity and Genetic Resources, University of Porto, Vairão, PortugalDepartment of Biology, Faculty of Sciences, University of Porto, Porto, PortugalBIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, Vairão, PortugalBiomedical Center (BMC), Core facility Animal Models (CAM), Faculty of Medicine, LMU München, Munich, GermanyCIBIO-InBIO, Research Center in Biodiversity and Genetic Resources, University of Porto, Vairão, PortugalDepartment of Biology, Faculty of Sciences, University of Porto, Porto, PortugalBIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, Vairão, PortugalCITS - Center of Investigation in Health Technologies, CESPU, Gandra, PortugalInstitute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, GermanyCIBIO-InBIO, Research Center in Biodiversity and Genetic Resources, University of Porto, Vairão, PortugalDepartment of Biology, Faculty of Sciences, University of Porto, Porto, PortugalBIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, Vairão, PortugalMax von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, GermanyGuanylate binding proteins (GBPs) are an evolutionarily ancient family of proteins that are widely distributed among eukaryotes. They belong to the dynamin superfamily of GTPases, and their expression can be partially induced by interferons (IFNs). GBPs are involved in the cell-autonomous innate immune response against bacterial, parasitic and viral infections. Evolutionary studies have shown that GBPs exhibit a pattern of gene gain and loss events, indicative for the birth-and-death model of evolution. Most species harbor large GBP gene clusters that encode multiple paralogs. Previous functional and in-depth evolutionary studies have mainly focused on murine and human GBPs. Since rabbits are another important model system for studying human diseases, we focus here on lagomorphs to broaden our understanding of the multifunctional GBP protein family by conducting evolutionary analyses and performing a molecular and functional characterization of rabbit GBPs. We observed that lagomorphs lack GBP3, 6 and 7. Furthermore, Leporidae experienced a loss of GBP2, a unique duplication of GBP5 and a massive expansion of GBP4. Gene expression analysis by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and transcriptome data revealed that leporid GBP expression varied across tissues. Overexpressed rabbit GBPs localized either uniformly and/or discretely to the cytoplasm and/or to the nucleus. Oryctolagus cuniculus (oc)GBP5L1 and rarely ocGBP5L2 were an exception, colocalizing with the trans-Golgi network (TGN). In addition, four ocGBPs were IFN-inducible and only ocGBP5L2 inhibited furin activity. In conclusion, from an evolutionary perspective, lagomorph GBPs experienced multiple gain and loss events, and the molecular and functional characteristics of ocGBP suggest a role in innate immunity.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1303089/fullGBPevolutioninnate immunityantiviral proteinscross-species conservationlagomorphs |
| spellingShingle | Luca Schelle João Vasco Côrte-Real João Vasco Côrte-Real João Vasco Côrte-Real João Vasco Côrte-Real Sharmeen Fayyaz Sharmeen Fayyaz Augusto del Pozo Ben Margarita Shnipova Moritz Petersen Rishikesh Lotke Bhavna Menon Dana Matzek Lena Pfaff Ana Pinheiro Ana Pinheiro João Pedro Marques João Pedro Marques João Pedro Marques José Melo-Ferreira José Melo-Ferreira José Melo-Ferreira Bastian Popper Pedro José Esteves Pedro José Esteves Pedro José Esteves Pedro José Esteves Daniel Sauter Joana Abrantes Joana Abrantes Joana Abrantes Hanna-Mari Baldauf Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions Frontiers in Immunology GBP evolution innate immunity antiviral proteins cross-species conservation lagomorphs |
| title | Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions |
| title_full | Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions |
| title_fullStr | Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions |
| title_full_unstemmed | Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions |
| title_short | Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions |
| title_sort | evolutionary and functional characterization of lagomorph guanylate binding proteins a story of gain and loss and shedding light on expression localization and innate immunity related functions |
| topic | GBP evolution innate immunity antiviral proteins cross-species conservation lagomorphs |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1303089/full |
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