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

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

  • EMBO J. 2018 Feb 15;37(4):e97840. doi: 10.15252/embj.201797840.
Katherine Fletcher 1,  Rachel Ulferts 2,  Elise Jacquin 1,  Talitha Veith 2,  Noor Gammoh 3,  Julia M Arasteh 4,  Ulrike Mayer 5,  Simon R Carding 6,  Thomas Wileman 4,  Rupert Beale 7,  Oliver Florey 8
Affiliations

Affiliations

  • 1 Signalling Programme, Babraham Institute, Cambridge, UK.
  • 2 Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.
  • 3 Edinburgh Cancer Research UK Centre University of Edinburgh, Edinburgh, UK.
  • 4 Norwich Medical School, UEA, Norwich, UK.
  • 5 School of Biological Sciences, UEA, Norwich, UK.
  • 6 Quadrum Institute Bioscience, Norwich Research Park, Norwich, UK.
  • 7 Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK rclb2@cam.ac.uk Oliver.Florey@babraham.ac.uk.
  • 8 Signalling Programme, Babraham Institute, Cambridge, UK rclb2@cam.ac.uk Oliver.Florey@babraham.ac.uk.
PMID: 29317426 DOI: 10.15252/embj.201797840
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.

Keywords

ATG16L1; LC3; autophagy; influenza; phagocytosis.

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