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ToolsBone, Benjamin, Griffith, Luke, Jefferson, Matthew, Yamauchi, Yohei, Wileman, Thomas and Powell, Penny P. (2025) ATG16L1 WD domain and linker regulates lipid trafficking to maintain plasma membrane integrity to limit influenza virus infection. Autophagy. ISSN 1554-8627
Full text not available from this repository. (Request a copy)Abstract
The non-canonical functions of autophagy protein ATG16L1 are dependent on a C-terminal WD domain. Recent studies show that the WD domain is required for conjugation of LC3 to single membranes during endocytosis and phagocytosis, where it is thought to promote fusion with lysosomes. Studies in cells lacking the WD domain suggest additional roles in the regulation of cytokine receptor recycling and plasma membrane repair. The WD domain also protects mice against lethal influenza virus in vivo. Here, analysis of mice lacking the WD domain (ΔWD) shows enrichment of cholesterol in brain tissue suggesting a role for the WD domain in cholesterol transport. Brain tissue and cells from ΔWD mice showed reduced cholesterol and phosphatidylserine (PS) in the plasma membrane. Cells from ΔWD mice also showed an intracellular accumulation of cholesterol predominantly in late endosomes. Infection studies using IAV suggest that the loss of cholesterol and PS from the plasma membrane in cells from ΔWD mice results in increased endocytosis and nuclear delivery of IAV, as well as increased Ifnb/Ifnβ and Isg15 gene expression. Upregulation of Il6, Ifnb and Isg15 mRNA were observed in “ex vivo” precision cut lung slices from ΔWD mice both at rest and in response to IAV infection. Overall, we present evidence that regulation of lipid transport by the WD domain of ATG16L1 may have downstream implications in attenuating viral infection and limiting lethal cytokine signaling.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding information: The work was supported by the Biotechnology and Biological Sciences Research Council [BB/M011216/1]; Biotechnology and Biological Sciences Research Council [BB/R00904X/1]; Medical Research Council [MR/R015937/1]. |
| Uncontrolled Keywords: | atg16l1 wd domain,cholesterol,cytokine storm,influenza virus,interferon,non-canonical autophagy,molecular biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1312 |
| 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 > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 29 Apr 2025 15:33 |
| Last Modified: | 06 May 2025 08:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/99145 |
| DOI: | 10.1080/15548627.2025.2482516 |
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