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

(2015) JOURNAL OF CELL BIOLOGY. 210(7). p.1133-1152
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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.
Keywords
UBIQUITINATED PROTEINS, DENDRITIC CELL MATURATION, ANTIGEN PRESENTATION, GENE-EXPRESSION, MACROPHAGES, MONOCYTES, IMMUNITY, MOUSE, LC3, PHOSPHORYLATION

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Citation

Please use this url to cite or link to this publication:

Chicago
Terawaki, Seigo, Voahirana Camosseto, Francesca Prete, Till Wenger, Alexia Papadopoulos, Christiane Rondeau, Alexis Combes, et al. 2015. “RUN and FYVE Domain-containing Protein 4 Enhances Autophagy and Lysosome Tethering in Response to Interleukin-4.” Journal of Cell Biology 210 (7): 1133–1152.
APA
Terawaki, S., Camosseto, V., Prete, F., Wenger, T., Papadopoulos, A., Rondeau, C., Combes, A., et al. (2015). RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4. JOURNAL OF CELL BIOLOGY, 210(7), 1133–1152.
Vancouver
1.
Terawaki S, Camosseto V, Prete F, Wenger T, Papadopoulos A, Rondeau C, et al. RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4. JOURNAL OF CELL BIOLOGY. 2015;210(7):1133–52.
MLA
Terawaki, Seigo, Voahirana Camosseto, Francesca Prete, et al. “RUN and FYVE Domain-containing Protein 4 Enhances Autophagy and Lysosome Tethering in Response to Interleukin-4.” JOURNAL OF CELL BIOLOGY 210.7 (2015): 1133–1152. Print.
@article{6973793,
  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.},
  author       = {Terawaki, Seigo and Camosseto, Voahirana and Prete, Francesca and Wenger, Till and Papadopoulos, Alexia and Rondeau, Christiane and Combes, Alexis and Rodriguez Rodrigues, Christian and Manh, Thien-Phong Vu and Fallet, Mathieu and English, Luc and Santamaria, Rodrigo and Soares, Ana R and Weil, Tobias and Hammad, Hamida and Desjardins, Michel and Gorvel, Jean-Pierre and Santos, Manuel AS and Gatti, Evelina and Pierre, Philippe},
  issn         = {0021-9525},
  journal      = {JOURNAL OF CELL BIOLOGY},
  language     = {eng},
  number       = {7},
  pages        = {1133--1152},
  title        = {RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4},
  url          = {http://dx.doi.org/10.1083/jcb.201501059},
  volume       = {210},
  year         = {2015},
}

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