title: RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4.
abstract: Autophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. Rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. Here, we unravel the role of RUN and FYVE domain-containing protein 4 (RUFY4) as a positive molecular regulator of macroautophagy in primary dendritic cells (DCs). We show that exposure to interleukin-4 (IL-4) during DC differentiation enhances autophagy flux through mTORC1 regulation and RUFY4 induction, which in turn actively promote LC3 degradation, Syntaxin 17-positive autophagosome formation, and lysosome tethering. Enhanced autophagy boosts endogenous antigen presentation by MHC II and allows host control of Brucella abortus replication in IL-4-treated DCs and in RUFY4-expressing cells. RUFY4 is therefore the first molecule characterized to date that promotes autophagy and influences endosome dynamics in a subset of immune cells.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France.
authors.forename: Seigo
authors.initials: S
authors.lastname: Terawaki
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France.
authors.forename: Voahirana
authors.initials: V
authors.lastname: Camosseto
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Prete
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France.
authors.forename: Till
authors.initials: T
authors.lastname: Wenger
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France.
authors.forename: Alexia
authors.initials: A
authors.lastname: Papadopoulos
authors.affiliation: Département de pathologie et biologie cellulaire, Université de Montréal, Québec H3C 3J7, Canada.
authors.forename: Christiane
authors.initials: C
authors.lastname: Rondeau
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Combes
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Rodriguez Rodrigues
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France.
authors.forename: Thien-Phong
authors.initials: TP
authors.lastname: Vu Manh
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Fallet
authors.affiliation: Département de pathologie et biologie cellulaire, Université de Montréal, Québec H3C 3J7, Canada.
authors.forename: Luc
authors.initials: L
authors.lastname: English
authors.affiliation: Departamento de Informática y Automática, Universidad de Salamanca, 37008 Salamanca, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Santamaria
authors.affiliation: RNA Biology Laboratory, Department of Biology and Centre for Environmental and Marine Studies (CESAM), University of Aveiro, 3810-193 Aveiro, Portugal Institute for Research in Biomedicine (iBiMED), Aveiro Health Sciences Program, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Soares
authors.affiliation: RNA Biology Laboratory, Department of Biology and Centre for Environmental and Marine Studies (CESAM), University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weil
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Department for Molecular Biomedical Research, VIB, Ghent 9050, Belgium.
authors.forename: Hamida
authors.initials: H
authors.lastname: Hammad
authors.affiliation: Département de pathologie et biologie cellulaire, Université de Montréal, Québec H3C 3J7, Canada Département de microbiologie, infectiologie, et immunologie, Université de Montréal, Québec H3C 3J7, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Desjardins
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
authors.affiliation: RNA Biology Laboratory, Department of Biology and Centre for Environmental and Marine Studies (CESAM), University of Aveiro, 3810-193 Aveiro, Portugal Institute for Research in Biomedicine (iBiMED), Aveiro Health Sciences Program, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Manuel A S
authors.initials: MA
authors.lastname: Santos
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France Institute for Research in Biomedicine (iBiMED), Aveiro Health Sciences Program, University of Aveiro, 3810-193 Aveiro, Portugal pierre@ciml.univ-mrs.fr gatti@ciml.univ-mrs.fr.
authors.forename: Evelina
authors.initials: E
authors.lastname: Gatti
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale U1104, Centre National de la Recherche Scientifique UMR7280, 13288 Marseille, France Institute for Research in Biomedicine (iBiMED), Aveiro Health Sciences Program, University of Aveiro, 3810-193 Aveiro, Portugal pierre@ciml.univ-mrs.fr gatti@ciml.univ-mrs.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pierre
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000276:immunology*; D002003:Brucella abortus / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D008247:Lysosomes / Q000235:genetics / Q000276:immunology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology; D046912:Multiprotein Complexes / Q000235:genetics / Q000276:immunology; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D050765:Qa-SNARE Proteins; C578013:Stx17 protein, mouse; D015847:Interleukin-4; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases