Tools
Tools
Serramito-Gómez, Inmaculada, Boada-Romero, Emilio, Villamuera, Raquel, Fernández-Cabrera, Álvaro, Cedillo, José Luis, Martín-Regalado, Ángela, Carding, Simon, Mayer, Uli 
ORCID: https://orcid.org/0000-0003-2328-0052, Powell, Penny P. ORCID: https://orcid.org/0000-0002-5347-0490, Wileman, Thomas, García-Higuera, Irene and Pimentel-Muiños, Felipe X.
(2020)
Regulation of cytokine signaling through direct interaction between cytokine receptors and the ATG16L1 WD40 domain.
Nature Communications, 11 (1).
ISSN 2041-1723
Preview |
PDF (Published_Version)
- Published Version
Available under License Creative Commons Attribution. Download (4MB) | Preview |
Abstract
ATG16L1, an autophagy mediator that specifies the site of LC3 lipidation, includes a C-terminal domain formed by 7 WD40-type repeats (WD40 domain, WDD), the function of which is unclear. Here we show that the WDD interacts with the intracellular domain of cytokine receptors to regulate their signaling output in response to ligand stimulation. Using a refined version of a previously described WDD-binding amino acid motif, here we show that this element is present in the intracellular domain of cytokine receptors. Two of these receptors, IL-10RB and IL-2Rγ, recognize the WDD through the motif and exhibit WDD-dependent LC3 lipidation activity. IL-10 promotes IL-10RB/ATG16L1 interaction through the WDD, and IL-10 signaling is suboptimal in cells lacking the WDD owing to delayed endocytosis and inefficient early trafficking of IL10/IL-10R complexes. Our data reveal WDD-dependent roles of ATG16L1 in the regulation of cytokine receptor trafficking and signaling, and provide a WDD-binding motif that might be used to identify additional WDD activators.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 28 Nov 2020 00:50 |
| Last Modified: | 19 Oct 2023 02:50 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/77827 |
| DOI: | 10.1038/s41467-020-19670-4 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |