Advanced search
1 file | 4.10 MB

Physical and functional interaction between A20 and ATG16L1-WD40 domain in the control of intestinal homeostasis

Author
Organization
Abstract
Prevention of inflammatory bowel disease (IBD) relies on tight control of inflammatory, cell death and autophagic mechanisms, but how these pathways are integrated at the molecular level is still unclear. Here we show that the anti-inflammatory protein A20 and the critical autophagic mediator Atg16l1 physically interact and synergize to regulate the stability of the intestinal epithelial barrier. A proteomic screen using the WD40 domain of ATG16L1 (WDD) identified A20 as a WDD-interacting protein. Loss of A20 and Atg16l1 in mouse intestinal epithelium induces spontaneous IBD-like pathology, as characterized by severe inflammation and increased intestinal epithelial cell death in both small and large intestine. Mechanistically, absence of A20 promotes Atg16l1 accumulation, while elimination of Atg16l1 or expression of WDD-deficient Atg16l1 stabilizes A20. Collectively our data show that A20 and Atg16l1 cooperatively control intestinal homeostasis by acting at the intersection of inflammatory, autophagy and cell death pathways.
Keywords
General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry

Downloads

  • 4145 19Slowicka.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 4.10 MB

Citation

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

Chicago
Slowicka, Karolina, Inmaculada Serramito-Gómez, Emilio Boada-Romero, Arne Martens, Mozes Sze, Ioanna Petta, Hanna-Kaisa Vikkula, et al. 2019. “Physical and Functional Interaction Between A20 and ATG16L1-WD40 Domain in the Control of Intestinal Homeostasis.” Nature Communications 10.
APA
Slowicka, K., Serramito-Gómez, I., Boada-Romero, E., Martens, A., Sze, M., Petta, I., Vikkula, H.-K., et al. (2019). Physical and functional interaction between A20 and ATG16L1-WD40 domain in the control of intestinal homeostasis. NATURE COMMUNICATIONS, 10.
Vancouver
1.
Slowicka K, Serramito-Gómez I, Boada-Romero E, Martens A, Sze M, Petta I, et al. Physical and functional interaction between A20 and ATG16L1-WD40 domain in the control of intestinal homeostasis. NATURE COMMUNICATIONS. 2019;10.
MLA
Slowicka, Karolina et al. “Physical and Functional Interaction Between A20 and ATG16L1-WD40 Domain in the Control of Intestinal Homeostasis.” NATURE COMMUNICATIONS 10 (2019): n. pag. Print.
@article{8613451,
  abstract     = {Prevention of inflammatory bowel disease (IBD) relies on tight control of inflammatory, cell death and autophagic mechanisms, but how these pathways are integrated at the molecular level is still unclear. Here we show that the anti-inflammatory protein A20 and the critical autophagic mediator Atg16l1 physically interact and synergize to regulate the stability of the intestinal epithelial barrier. A proteomic screen using the WD40 domain of ATG16L1 (WDD) identified A20 as a WDD-interacting protein. Loss of A20 and Atg16l1 in mouse intestinal epithelium induces spontaneous IBD-like pathology, as characterized by severe inflammation and increased intestinal epithelial cell death in both small and large intestine. Mechanistically, absence of A20 promotes Atg16l1 accumulation, while elimination of Atg16l1 or expression of WDD-deficient Atg16l1 stabilizes A20. Collectively our data show that A20 and Atg16l1 cooperatively control intestinal homeostasis by acting at the intersection of inflammatory, autophagy and cell death pathways.},
  articleno    = {1834},
  author       = {Slowicka, Karolina and Serramito-Gómez, Inmaculada and Boada-Romero, Emilio and Martens, Arne and Sze, Mozes and Petta, Ioanna and Vikkula, Hanna-Kaisa and De Rycke, Riet and Parthoens, Eef and Lippens, Saskia and Savvides, Savvas and Wullaert, Andy and Vereecke, Lars and Pimentel-Muiños, Felipe X and van Loo, Geert},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {General Biochemistry,Genetics and Molecular Biology,General Physics and Astronomy,General Chemistry},
  language     = {eng},
  pages        = {15},
  title        = {Physical and functional interaction between A20 and ATG16L1-WD40 domain in the control of intestinal homeostasis},
  url          = {http://dx.doi.org/10.1038/s41467-019-09667-z},
  volume       = {10},
  year         = {2019},
}

Altmetric
View in Altmetric