RRC ID 36008
Author Terawaki S, Camosseto V, Prete F, Wenger T, Papadopoulos A, Rondeau C, Combes A, Rodriguez Rodrigues C, Vu Manh TP, Fallet M, English L, Santamaria R, Soares AR, Weil T, Hammad H, Desjardins M, Gorvel JP, Santos MA, Gatti E, Pierre P.
Title RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4.
Journal J Cell Biol
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.
Volume 210(7)
Pages 1133-52
Published 2015-9-28
DOI 10.1083/jcb.201501059
PII jcb.201501059
PMID 26416964
PMC PMC4586740
MeSH Animals Autophagy / genetics Autophagy / immunology* Brucella abortus / immunology Dendritic Cells / cytology Dendritic Cells / immunology* Interleukin-4 / genetics Interleukin-4 / immunology* Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / immunology* Lysosomes / genetics Lysosomes / immunology* Mechanistic Target of Rapamycin Complex 1 Mice Mice, Knockout Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / immunology Multiprotein Complexes / genetics Multiprotein Complexes / immunology Qa-SNARE Proteins / genetics Qa-SNARE Proteins / immunology TOR Serine-Threonine Kinases / genetics TOR Serine-Threonine Kinases / immunology
IF 8.811
Times Cited 29
Mice RBRC00806