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

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.

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  • Authors+Show Affiliations

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    Signalling Programme, Babraham Institute, Cambridge, UK.

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    Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.

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    Signalling Programme, Babraham Institute, Cambridge, UK.

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    Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.

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    Edinburgh Cancer Research UK Centre University of Edinburgh, Edinburgh, UK.

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    Norwich Medical School, UEA, Norwich, UK.

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    School of Biological Sciences, UEA, Norwich, UK.

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    Quadrum Institute Bioscience, Norwich Research Park, Norwich, UK.

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    Norwich Medical School, UEA, Norwich, UK.

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    Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK rclb2@cam.ac.uk Oliver.Florey@babraham.ac.uk.

    Signalling Programme, Babraham Institute, Cambridge, UK rclb2@cam.ac.uk Oliver.Florey@babraham.ac.uk.

    Source

    The EMBO journal 37:4 2018 Feb 15 pg

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    29317426