The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes.
EMBO J
; 37(4)2018 02 15.
Article
en En
| MEDLINE
| ID: mdl-29317426
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Autofagia
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Proteínas Portadoras
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Proteínas Relacionadas con la Autofagia
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Repeticiones WD40
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Membranas Intracelulares
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Lípidos de la Membrana
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Proteínas Asociadas a Microtúbulos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
EMBO J
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido