RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4
| Autor: | Jean-Pierre Gorvel, Hamida Hammad, Manuel A. S. Santos, Ana R. Soares, Evelina Gatti, Alexis J. Combes, Michel Desjardins, Francesca Prete, Christiane Rondeau, Mathieu Fallet, Thien-Phong Vu Manh, Rodrigo Santamaría, Luc English, Christian Rodriguez Rodrigues, Philippe Pierre, Tobias Weil, Till Wenger, Voahirana Camosseto, Seigo Terawaki, Alexia Papadopoulos |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Endosome
Antigen presentation Brucella abortus mTORC1 Biology Mechanistic Target of Rapamycin Complex 1 IMMUNITY BAG3 MOUSE Article DENDRITIC CELL MATURATION Mice Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA Lysosome medicine Autophagy Medicine and Health Sciences ANTIGEN PRESENTATION LC3 Animals UBIQUITINATED PROTEINS MACROPHAGES PHOSPHORYLATION Interleukin 4 Research Articles GENE-EXPRESSION Mice Knockout Qa-SNARE Proteins TOR Serine-Threonine Kinases Intracellular Signaling Peptides and Proteins Cell Biology Dendritic Cells 3. Good health Cell biology medicine.anatomical_structure Biochemistry MONOCYTES Multiprotein Complexes FYVE domain Interleukin-4 Lysosomes Microtubule-Associated Proteins |
| Zdroj: | JOURNAL OF CELL BIOLOGY Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP research@ua; Vol 6 (2015); 40 research@ua; vol. 6 (2015); 40 The Journal of Cell Biology |
| ISSN: | 0021-9525 2182-9357 |
| Popis: | Interleukin-4 boosts the capacity of dendritic cells to present endogenous antigens on MHC II and to resist bacterial infection through a mechanism shown to be partially dependent on RUFY4 expression. 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. |
| Databáze: | OpenAIRE |
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