학술논문
RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4.
Document Type
Article
Author
Terawaki, Seigo; Camosseto, Voahirana; Prête, Francesco; Wenger, Till; Papadopoulos, Alexia; Rondeau, Christiane; Combes, Alexis; Rodrigues, Christian Rodriguez; Manh, Thien-Phong Vu; Fallet, Mathieu; English, Luc; Santamaria, Rodrigo; Soares, Ana R.; Weil, Tobias; Hammad, Hamida; Desjardins, Michel; Gorvel, Jean-Pierre; Santos, Manuel A. S.; Gatti, Evelina; Pierre, Philippe
Source
Subject
*AUTOPHAGY
*LYSOSOMES
*INTERLEUKIN-4
*DENDRITIC cells
*ENDOSOMES
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Language
ISSN
0021-9525
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 mTORCl 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 MHCII 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. [ABSTRACT FROM AUTHOR]