RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes.

Autor: Char R; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France., Liu Z; School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, PR China., Jacqueline C; Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR1064, F-44000, Nantes, France., Davieau M; Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR1064, F-44000, Nantes, France., Delgado MG; INSERM U932, Institut Curie, ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043, Paris, France., Soufflet C; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France., Fallet M; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France., Chasson L; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France., Chapuy R; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France., Camosseto V; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France., Strock E; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France., Rua R; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France., Almeida CR; Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal., Su B; Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China., Lennon-Duménil AM; INSERM U932, Institut Curie, ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043, Paris, France., Nal B; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France., Roquilly A; Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR1064, F-44000, Nantes, France., Liang Y; School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, PR China., Méresse S; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France., Gatti E; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France. gatti@ciml.univ-mrs.fr.; Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal. gatti@ciml.univ-mrs.fr., Pierre P; Aix Marseille Université, CNRS, INSERM, CIML, 13288, Marseille, cedex 9, France. pierre@ciml.univ-mrs.fr.; Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal. pierre@ciml.univ-mrs.fr.; Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China. pierre@ciml.univ-mrs.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jul 18; Vol. 14 (1), pp. 4290. Date of Electronic Publication: 2023 Jul 18.
DOI: 10.1038/s41467-023-40062-x
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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