Evidence map›Paper›PMID 34706226›Full record

ArticleCell reports2021

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

Rachel Ulferts, Elena Marcassa, Lewis Timimi, Liam Changwoo Lee, Andrew Daley, Beatriz Montaner, Suzanne Dawn Turner, Oliver Florey, John Kenneth Baillie, Rupert Beale

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
6.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
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  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. ATG16L1 controls mammalian vacuolar proton ATPase.The Journal of cell biology · 2025
    Article
  13. Article
  14. Article
  15. Autophagy Protease ATG4D Facilitates Proliferation and Malignancy of Osteosarcoma Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. cGAS-STING: mechanisms and therapeutic opportunities.Science China. Life sciences · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Rachel UlfertsThe Francis Crick Institute, London, UK; Department of Pathology, University of Cambridge, Cambridge, UK. Electronic address: rachel.ulferts@crick.ac.uk.
Elena MarcassaThe Francis Crick Institute, London, UK.
Lewis TimimiThe Francis Crick Institute, London, UK.
Liam Changwoo LeeDepartment of Pathology, University of Cambridge, Cambridge, UK.
Andrew DaleyDepartment of Pathology, University of Cambridge, Cambridge, UK.
Beatriz MontanerThe Francis Crick Institute, London, UK.
Suzanne Dawn TurnerDepartment of Pathology, University of Cambridge, Cambridge, UK.
Oliver FloreySignalling Programme, Babraham Institute, Cambridge, UK.
John Kenneth BaillieUniversity of Edinburgh, Edinburgh, UK. Electronic address: j.k.baillie@ed.ac.uk.
Rupert BealeThe 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.
University of Cambridge · GBThe Francis Crick Institute · GBBabraham Institute · GBUniversity of Edinburgh · GB

Funding

Cancer Research UK FC001827Medical Research Council FC001827Medical Research Council MR/M00869X/1Medical Research Council MR/M00869X/2Wellcome Trust FC001827
6 · The paper itself

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.

Indexed as

Autophagy-Related ProteinsLipoylationMicrotubule-Associated ProteinsAutophagosomesCRISPR-Cas SystemsHCT116 CellsHEK293 CellsHumansInfluenza A virusSalmonellaViral Matrix ProteinsViroporin ProteinsATG16L1 protein, humanAutophagy-Related ProteinsM2 protein, Influenza A virusMAP1LC3A protein, humanMicrotubule-Associated ProteinsViral Matrix ProteinsViroporin ProteinsATG16L1ATG4DautophagyinfluenzaRALGAPv-ATPase

Identifiers

PMID34706226
PMCPMC8567314
OpenAlexW3208400701

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.