RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes
Abstract Endo-lysosomes transport along microtubules and clustering in the perinuclear area are two necessary steps for microbes to activate specialized phagocyte functions. We report that RUN and FYVE domain-containing protein 3 (RUFY3) exists as two alternative isoforms distinguishable by the pres...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40062-x |
| _version_ | 1797774079103598592 |
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| author | Rémy Char Zhuangzhuang Liu Cédric Jacqueline Marion Davieau Maria-Graciela Delgado Clara Soufflet Mathieu Fallet Lionel Chasson Raphael Chapuy Voahirana Camosseto Eva Strock Rejane Rua Catarina R. Almeida Bing Su Ana-Maria Lennon-Duménil Beatrice Nal Antoine Roquilly Yinming Liang Stéphane Méresse Evelina Gatti Philippe Pierre |
| author_facet | Rémy Char Zhuangzhuang Liu Cédric Jacqueline Marion Davieau Maria-Graciela Delgado Clara Soufflet Mathieu Fallet Lionel Chasson Raphael Chapuy Voahirana Camosseto Eva Strock Rejane Rua Catarina R. Almeida Bing Su Ana-Maria Lennon-Duménil Beatrice Nal Antoine Roquilly Yinming Liang Stéphane Méresse Evelina Gatti Philippe Pierre |
| author_sort | Rémy Char |
| collection | DOAJ |
| description | Abstract Endo-lysosomes transport along microtubules and clustering in the perinuclear area are two necessary steps for microbes to activate specialized phagocyte functions. We report that RUN and FYVE domain-containing protein 3 (RUFY3) exists as two alternative isoforms distinguishable by the presence of a C-terminal FYVE domain and by their affinity for phosphatidylinositol 3-phosphate on endosomal membranes. The FYVE domain-bearing isoform (iRUFY3) is preferentially expressed in primary immune cells and up-regulated upon activation by microbes and Interferons. iRUFY3 is necessary for ARL8b + /LAMP1+ endo-lysosomes positioning in the pericentriolar organelles cloud of LPS-activated macrophages. We show that iRUFY3 controls macrophages migration, MHC II presentation and responses to Interferon-γ, while being important for intracellular Salmonella replication. Specific inactivation of rufy3 in phagocytes leads to aggravated pathologies in mouse upon LPS injection or bacterial pneumonia. This study highlights the role of iRUFY3 in controlling endo-lysosomal dynamics, which contributes to phagocyte activation and immune response regulation. |
| first_indexed | 2024-03-12T22:15:48Z |
| format | Article |
| id | doaj.art-4a23f4a1b15044b5bbac175e040f08dd |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-12T22:15:48Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-4a23f4a1b15044b5bbac175e040f08dd2023-07-23T11:18:28ZengNature PortfolioNature Communications2041-17232023-07-0114112010.1038/s41467-023-40062-xRUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytesRémy Char0Zhuangzhuang Liu1Cédric Jacqueline2Marion Davieau3Maria-Graciela Delgado4Clara Soufflet5Mathieu Fallet6Lionel Chasson7Raphael Chapuy8Voahirana Camosseto9Eva Strock10Rejane Rua11Catarina R. Almeida12Bing Su13Ana-Maria Lennon-Duménil14Beatrice Nal15Antoine Roquilly16Yinming Liang17Stéphane Méresse18Evelina Gatti19Philippe Pierre20Aix Marseille Université, CNRS, INSERM, CIMLSchool of Laboratory Medicine, Xinxiang Medical UniversityNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational ImmunologyNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational ImmunologyINSERM U932, Institut CurieAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLInstitute of Biomedicine (iBiMED), Department of Medical Sciences, University of AveiroShanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of MedicineINSERM U932, Institut CurieAix Marseille Université, CNRS, INSERM, CIMLNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational ImmunologySchool of Laboratory Medicine, Xinxiang Medical UniversityAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAix Marseille Université, CNRS, INSERM, CIMLAbstract Endo-lysosomes transport along microtubules and clustering in the perinuclear area are two necessary steps for microbes to activate specialized phagocyte functions. We report that RUN and FYVE domain-containing protein 3 (RUFY3) exists as two alternative isoforms distinguishable by the presence of a C-terminal FYVE domain and by their affinity for phosphatidylinositol 3-phosphate on endosomal membranes. The FYVE domain-bearing isoform (iRUFY3) is preferentially expressed in primary immune cells and up-regulated upon activation by microbes and Interferons. iRUFY3 is necessary for ARL8b + /LAMP1+ endo-lysosomes positioning in the pericentriolar organelles cloud of LPS-activated macrophages. We show that iRUFY3 controls macrophages migration, MHC II presentation and responses to Interferon-γ, while being important for intracellular Salmonella replication. Specific inactivation of rufy3 in phagocytes leads to aggravated pathologies in mouse upon LPS injection or bacterial pneumonia. This study highlights the role of iRUFY3 in controlling endo-lysosomal dynamics, which contributes to phagocyte activation and immune response regulation.https://doi.org/10.1038/s41467-023-40062-x |
| spellingShingle | Rémy Char Zhuangzhuang Liu Cédric Jacqueline Marion Davieau Maria-Graciela Delgado Clara Soufflet Mathieu Fallet Lionel Chasson Raphael Chapuy Voahirana Camosseto Eva Strock Rejane Rua Catarina R. Almeida Bing Su Ana-Maria Lennon-Duménil Beatrice Nal Antoine Roquilly Yinming Liang Stéphane Méresse Evelina Gatti Philippe Pierre RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes Nature Communications |
| title | RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes |
| title_full | RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes |
| title_fullStr | RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes |
| title_full_unstemmed | RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes |
| title_short | RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes |
| title_sort | rufy3 regulates endolysosomes perinuclear positioning antigen presentation and migration in activated phagocytes |
| url | https://doi.org/10.1038/s41467-023-40062-x |
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