The WD40 domain of ATG16L1 is required for its non‐canonical role in lipidation of LC3 at single membranes

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Fletcher, Katherine, Ulferts, Rachel, Jacquin, Elise, Veith, Tabitha, Gammoh, Noor, Arasteh, Julia M, Mayer, Ulrike ORCID: https://orcid.org/0000-0003-2328-0052, Carding, Simon, Wileman, Thomas, Beale, Rupert and Florey, Oliver (2018) The WD40 domain of ATG16L1 is required for its non‐canonical role in lipidation of LC3 at single membranes. The EMBO Journal, 37 (4). ISSN 0261-4189

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Abstract

A hallmark of macroautophagy is the covalent lipidation of LC3 and insertion into the double‐membrane phagophore, which is driven by the ATG16L1/ATG5‐ATG12 complex. In contrast, non‐canonical autophagy is a pathway through which LC3 is lipidated and inserted into single membranes, particularly endolysosomal vacuoles during cell engulfment events such as LC3‐associated phagocytosis. Factors controlling the targeting of ATG16L1 to phagophores are dispensable for non‐canonical autophagy, for which the mechanism of ATG16L1 recruitment is unknown. Here we show that the WD repeat‐containing C‐terminal domain (WD40 CTD) of ATG16L1 is essential for LC3 recruitment to endolysosomal membranes during non‐canonical autophagy, but dispensable for canonical autophagy. Using this strategy to inhibit non‐canonical autophagy specifically, we show a reduction of MHC class II antigen presentation in dendritic cells from mice lacking the WD40 CTD. Further, we demonstrate activation of non‐canonical autophagy dependent on the WD40 CTD during influenza A virus infection. This suggests dependence on WD40 CTD distinguishes between macroautophagy and non‐canonical use of autophagy machinery.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > The Sainsbury Laboratory
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Depositing User: Pure Connector
Date Deposited: 22 Jan 2018 13:30
Last Modified: 19 Oct 2023 02:08
URI: https://ueaeprints.uea.ac.uk/id/eprint/66030
DOI: 10.15252/embj.201797840

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