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J Cell Biol. 2015 Sep 28;210(7):1133-52. doi: 10.1083/jcb.201501059.

RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4.

Author information

1
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.
2
Département de pathologie et biologie cellulaire, Université de Montréal, Québec H3C 3J7, Canada.
3
Departamento de Informática y Automática, Universidad de Salamanca, 37008 Salamanca, Spain.
4
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.
5
RNA Biology Laboratory, Department of Biology and Centre for Environmental and Marine Studies (CESAM), University of Aveiro, 3810-193 Aveiro, Portugal.
6
Laboratory of Immunoregulation and Mucosal Immunology, Department for Molecular Biomedical Research, VIB, Ghent 9050, Belgium.
7
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.
8
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.

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.

PMID:
26416964
PMCID:
PMC4586740
DOI:
10.1083/jcb.201501059
[Indexed for MEDLINE]
Free PMC Article

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