Subtractive CRISPR screen identifies the ATG16L1/vacuolar ATPase axis as required for non-canonical LC3 lipidation.


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
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

109899

Subventions

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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Auteurs

Rachel Ulferts (R)

The Francis Crick Institute, London, UK; Department of Pathology, University of Cambridge, Cambridge, UK. Electronic address: rachel.ulferts@crick.ac.uk.

Elena Marcassa (E)

The Francis Crick Institute, London, UK.

Lewis Timimi (L)

The Francis Crick Institute, London, UK.

Liam Changwoo Lee (LC)

Department of Pathology, University of Cambridge, Cambridge, UK.

Andrew Daley (A)

Department of Pathology, University of Cambridge, Cambridge, UK.

Beatriz Montaner (B)

The Francis Crick Institute, London, UK.

Suzanne Dawn Turner (SD)

Department of Pathology, University of Cambridge, Cambridge, UK.

Oliver Florey (O)

Signalling Programme, Babraham Institute, Cambridge, UK.

John Kenneth Baillie (JK)

University of Edinburgh, Edinburgh, UK. Electronic address: j.k.baillie@ed.ac.uk.

Rupert Beale (R)

The Francis Crick Institute, London, UK; Department of Pathology, University of Cambridge, Cambridge, UK; Division of Medicine, UCL, London, UK. Electronic address: rupert.beale@crick.ac.uk.

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Classifications MeSH