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

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 RU N and FY VE domain-containing protein 3 (RUFY3) exists as two alternative isoforms distinguishable by the presence of...

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Published in:	Nature communications Vol. 14; no. 1; pp. 4290 - 20
Main Authors:	Char, Rémy, Liu, Zhuangzhuang, Jacqueline, Cédric, Davieau, Marion, Delgado, Maria-Graciela, Soufflet, Clara, Fallet, Mathieu, Chasson, Lionel, Chapuy, Raphael, Camosseto, Voahirana, Strock, Eva, Rua, Rejane, Almeida, Catarina R., Su, Bing, Lennon-Duménil, Ana-Maria, Nal, Beatrice, Roquilly, Antoine, Liang, Yinming, Méresse, Stéphane, Gatti, Evelina, Pierre, Philippe
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 18-07-2023 Nature Publishing Group Nature Portfolio
Subjects:	13/106 13/51 14/19 38 38/62 38/77 38/89 42/41 631/250/21/1293 631/80/313/1776 692/699/255/1318 82/1 96/31 Animals Antigen Presentation Antigens Autophagy Cell activation Clustering Cytoskeleton Endosomes - metabolism Humanities and Social Sciences Immune response Immune system Inactivation Isoforms Leukocyte migration Life Sciences Lipopolysaccharides Lipopolysaccharides - metabolism Lysosomes Lysosomes - metabolism Macrophages Major histocompatibility complex Mice Microorganisms Microtubules multidisciplinary Organelles Phagocytes Phagocytosis Phosphatidylinositol 3-phosphate Proteins Salmonella Science Science (multidisciplinary) γ-Interferon Bacterial infection Antigen-presenting cells Endosomes
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Summary:	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 RU N and FY VE 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. RUFY proteins are known to regulate autophagy, cytoskeletal dynamics, migration and endosomal trafficking. Here, Char et al. show that iRUFY3 plays a role in perinuclear positioning, phagocyte migration and antigen presentation during Salmonella infection.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-023-40062-x