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

Fletcher, K; Ulferts, R; Jacquin, E; Veith, T; Gammoh, N; Arasteh, JM; Mayer, U; ... Florey, O; + view all (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) , Article e97840. 10.15252/embj.201797840. Green open access

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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.

Type: Article
Title: The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embj.201797840
Publisher version: https://doi.org/10.15252/embj.201797840
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: ATG16L1, LC3, autophagy, influenza, phagocytosis, Animals, Antigen Presentation, Autophagy, Autophagy-Related Proteins, Carrier Proteins, Cells, Cultured, Class III Phosphatidylinositol 3-Kinases, Dendritic Cells, Endosomes, Female, Humans, Influenza A virus, Influenza, Human, Intracellular Membranes, Lysosomes, Membrane Lipids, Mice, Mice, Knockout, Microtubule-Associated Proteins, WD40 Repeats
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10082280
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