Ulferts, R; Marcassa, E; Timimi, L; Lee, LC; Daley, A; Montaner, B; Turner, SD; ... Beale, R; + view all Ulferts, R; Marcassa, E; Timimi, L; Lee, LC; Daley, A; Montaner, B; Turner, SD; Florey, O; Baillie, JK; Beale, R; - view fewer (2021) Subtractive CRISPR screen identifies the ATG16L1/vacuolar ATPase axis as required for non-canonical LC3 lipidation. Cell Reports , 37 (4) , Article 109899. 10.1016/j.celrep.2021.109899.

Preview

Text Beale_Subtractive CRISPR screen identifies the ATG16L1:vacuolar ATPase axis as required for non-canonical LC3 lipidation_VoR.pdf - Published Version Download (4MB) | Preview

Abstract

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.

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as XMLJSONCSV

Downloads by country - last 12 months

Export as CSVXMLJSON

Archive Staff Only

View Item