Subtractive CRISPR screen identifies the ATG16L1/vacuolar ATPase axis as required for non-canonical LC3 lipidation.
ATG16L1
ATG4D
RALGAP
autophagy
influenza
v-ATPase
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 10 2021
26 10 2021
Historique:
received:
01
09
2020
revised:
08
04
2021
accepted:
06
10
2021
entrez:
27
10
2021
pubmed:
28
10
2021
medline:
11
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34706226
pii: S2211-1247(21)01369-3
doi: 10.1016/j.celrep.2021.109899
pmc: PMC8567314
pii:
doi:
Substances chimiques
ATG16L1 protein, human
0
Autophagy-Related Proteins
0
M2 protein, Influenza A virus
0
MAP1LC3A protein, human
0
Microtubule-Associated Proteins
0
Viral Matrix Proteins
0
Viroporin Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109899Subventions
Organisme : Medical Research Council
ID : MR/M00869X/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001827
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001827
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M00869X/1
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001827
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001827
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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