Abstract / Description of output
Although commonly associated with autophagosomes, LC3 can also be recruited to membranes by covalent lipidation in a variety of non-canonical contexts. These include responses to ionophores such as the M2 proton channel of influenza A virus. We report a subtractive CRISPR screen that identifies factors required for non-canonical LC3 lipidation. As well as the enzyme complexes directly responsible for LC3 lipidation in all contexts, we show the RALGAP complex is important for M2-induced, but not ionophore drug-induced, LC3 lipidation. In contrast, ATG4D is responsible for LC3 recycling in M2-induced and basal LC3 lipidation. Identification of a vacuolar ATPase subunit in the screen suggests a common mechanism for non-canonical LC3 recruitment. Influenza-induced and ionophore drug-induced LC3 lipidation lead to association of the vacuolar ATPase and ATG16L1 and can be antagonized by Salmonella SopF. LC3 recruitment to erroneously neutral compartments may therefore represent a response to damage caused by diverse invasive pathogens.
Original language | English |
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Article number | 109899 |
Pages (from-to) | 1 - 11 |
Number of pages | 11 |
Journal | Cell Reports |
Volume | 37 |
Issue number | 4 |
Early online date | 26 Oct 2021 |
DOIs | |
Publication status | E-pub ahead of print - 26 Oct 2021 |
Keywords / Materials (for Non-textual outputs)
- Autophagosomes/genetics
- Autophagy-Related Proteins/genetics
- CRISPR-Cas Systems
- HCT116 Cells
- HEK293 Cells
- Humans
- Influenza A virus/genetics
- Lipoylation
- Microtubule-Associated Proteins/genetics
- Salmonella/genetics
- Viral Matrix Proteins/genetics
- Viroporin Proteins/genetics