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The WD 40 domain of ATG 16L1 is required for its non‐canonical role in lipidation of LC 3 at single membranes
Author(s) -
Fletcher Katherine,
Ulferts Rachel,
Jacquin Elise,
Veith Talitha,
Gammoh Noor,
Arasteh Julia M,
Mayer Ulrike,
Carding Simon R,
Wileman Thomas,
Beale Rupert,
Florey Oliver
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797840
Subject(s) - library science , art history , operations research , history , engineering , computer science
A hallmark of macroautophagy is the covalent lipidation of LC 3 and insertion into the double‐membrane phagophore, which is driven by the ATG 16L1/ ATG 5‐ ATG 12 complex. In contrast, non‐canonical autophagy is a pathway through which LC 3 is lipidated and inserted into single membranes, particularly endolysosomal vacuoles during cell engulfment events such as LC 3‐associated phagocytosis. Factors controlling the targeting of ATG 16L1 to phagophores are dispensable for non‐canonical autophagy, for which the mechanism of ATG 16L1 recruitment is unknown. Here we show that the WD repeat‐containing C‐terminal domain ( WD 40 CTD ) of ATG 16L1 is essential for LC 3 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 WD 40 CTD . Further, we demonstrate activation of non‐canonical autophagy dependent on the WD 40 CTD during influenza A virus infection. This suggests dependence on WD 40 CTD distinguishes between macroautophagy and non‐canonical use of autophagy machinery.