Evidence map›Paper›PMID 30767700›Full record

ArticleAutophagy2019

Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs.

Åsa Birna Birgisdottir, Stephane Mouilleron, Zambarlal Bhujabal, Martina Wirth, Eva Sjøttem, Gry Evjen, Wenxin Zhang, Rebecca Lee, Nicola O'Reilly, Sharon A Tooze and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 1 pooled it
10.4field-weighted citation impact, top 1% 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

78 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. The Human Autophagy Core Complexes.Annual review of biochemistry · 2026
    Review
  7. Review
  8. mBio · 2026
    Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. The human autophagy-initiating complexes ULK1C and PI3KC3-C1.The Journal of biological chemistry · 2025
    Review
  16. Review
  17. Article
  18. Review
  19. Mechanisms and roles of membrane-anchored ATG8s.Frontiers in cell and developmental biology · 2025
    Review
  20. Article

18 more citing papers are in PubMed but not listed here.

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

12 authors at 2 institutions in 2 countries.

Åsa Birna Birgisdottira Molecular Cancer Research Group, Department of Medical Biology , University of Tromsø -The Arctic University of Norway , Tromsø , Norway.
Stephane Mouilleronb Structural Biology , The Francis Crick Institute , London , UK.
Zambarlal Bhujabala Molecular Cancer Research Group, Department of Medical Biology , University of Tromsø -The Arctic University of Norway , Tromsø , Norway.
Martina Wirthc Molecular Cell Biology of Autophagy Laboratory , The Francis Crick Institute , London , UK.
Eva Sjøttema Molecular Cancer Research Group, Department of Medical Biology , University of Tromsø -The Arctic University of Norway , Tromsø , Norway.
Gry Evjena Molecular Cancer Research Group, Department of Medical Biology , University of Tromsø -The Arctic University of Norway , Tromsø , Norway.
Wenxin Zhangb Structural Biology , The Francis Crick Institute , London , UK.ORCID 0000-0002-7657-4495
Rebecca Leeb Structural Biology , The Francis Crick Institute , London , UK.
Nicola O'Reillyd Peptide Chemistry Science Technology Platform , The Francis Crick Institute , London , UK.
Sharon A Toozec Molecular Cell Biology of Autophagy Laboratory , The Francis Crick Institute , London , UK.ORCID 0000-0002-2182-3116
Trond Lamarka Molecular Cancer Research Group, Department of Medical Biology , University of Tromsø -The Arctic University of Norway , Tromsø , Norway.
Terje Johansena Molecular Cancer Research Group, Department of Medical Biology , University of Tromsø -The Arctic University of Norway , Tromsø , Norway.ORCID 0000-0003-1451-9578
The Francis Crick Institute · GBUiT The Arctic University of Norway · NO

Funding

Cancer Research UK 15153Cancer Research UK FC001187Cancer Research UK FC001999Medical Research Council FC001187Medical Research Council FC001999Wellcome Trust FC001187Wellcome Trust FC001999
6 · The paper itself

Abstract

Autophagosome formation depends on a carefully orchestrated interplay between membrane-associated protein complexes. Initiation of macroautophagy/autophagy is mediated by the ULK1 (unc-51 like autophagy activating kinase 1) protein kinase complex and the autophagy-specific class III phosphatidylinositol 3-kinase complex I (PtdIns3K-C1). The latter contains PIK3C3/VPS34, PIK3R4/VPS15, BECN1/Beclin 1 and ATG14 and phosphorylates phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns3P). Here, we show that PIK3C3, BECN1 and ATG14 contain functional LIR motifs and interact with the Atg8-family proteins with a preference for GABARAP and GABARAPL1. High resolution crystal structures of the functional LIR motifs of these core components of PtdIns3K-C1were obtained. Variation in hydrophobic pocket 2 (HP2) may explain the specificity for the GABARAP family. Mutation of the LIR motif in ATG14 did not prevent formation of the PtdIns3K-C1 complex, but blocked colocalization with MAP1LC3B/LC3B and impaired mitophagy. The ULK-mediated phosphorylation of S29 in ATG14 was strongly dependent on a functional LIR motif in ATG14. GABARAP-preferring LIR motifs in PIK3C3, BECN1 and ATG14 may, via coincidence detection, contribute to scaffolding of PtdIns3K-C1 on membranes for efficient autophagosome formation.

Indexed as

AutophagyAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAmino Acid MotifsAmino Acid SequenceApoptosis Regulatory ProteinsAutophagy-Related Protein 8 FamilyAutophagy-Related ProteinsBeclin-1Class III Phosphatidylinositol 3-KinasesHCT116 CellsHumansHydrophobic and Hydrophilic InteractionsMicrotubule-Associated ProteinsMitophagyModels, MolecularAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportApoptosis Regulatory ProteinsATG14 protein, humanAutophagy-Related Protein 8 FamilyAutophagy-Related ProteinsBeclin-1Class III Phosphatidylinositol 3-KinasesGABARAPL1 protein, humanGABARAP protein, humanMAP1LC3A protein, humanMicrotubule-Associated ProteinsPeptidesATG14AutophagyBECN1GABARAPLIRPIK3C3

Identifiers

PMID30767700
PMCPMC6613885
OpenAlexW2912599138

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.