Evidence map›Paper›PMID 42696573›Full record

ArticleScience advances2026

Reconstitution of multistep recruitment of ULK1 to membranes in autophagy.

Yongjia Duan, Ye Lu, Sanjoy Paul, Johannes Betz, Léa P Wilhelm, Annan S I Cook, Xuefeng Ren, Elias Adriaenssens, Sascha Martens, Ian G Ganley and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Yongjia DuanDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0009-0001-7553-0124
Ye LuDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0009-0001-6788-4205
Sanjoy PaulAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.ORCID 0000-0001-5040-8002
Johannes BetzDepartment of Theoretical Biophysics, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany.ORCID 0000-0003-0910-6576
Léa P WilhelmMRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, DD1 5EH, UK.ORCID 0000-0001-5926-4666
Annan S I CookDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0001-6415-9107
Xuefeng RenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0002-4822-4316
Elias AdriaenssensAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.ORCID 0000-0001-9430-917X
Sascha MartensAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.ORCID 0000-0003-3786-8199
Ian G GanleyAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.ORCID 0000-0003-1481-9407
Gerhard HummerAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.ORCID 0000-0001-7768-746X
James H HurleyDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0001-5054-5445

Funding

The autophagy core complexes in neuronal quality controlR01NS134598 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI James H Hurley · 2025 to 2026
$1.0M
NINDS NIH HHS R01 NS134598
6 · The paper itself

Abstract

The human Unc51-like kinase 1 (ULK1) autophagy-initiating complex consists of ULK1, FIP200, and the Hop/Rev7/Mad2 (HORMA) domain heterodimer ATG13:ATG101. Phosphatidylinositol 3-phosphate (PI3P) is essential to recruit ULK1 complex (ULK1C) to membranes for ULK1, but ULK1C subunits do not contain PI3P-binding domains. Here, we show that the ATG13:ATG101 dimer forms a complex with the PI3P-binding protein WD40 interacting with phosphoinositide protein 3 (WIPI3), as well as WIPI2. Bound to WIPI2 and WIPI3, ATG13:ATG101 inserts its Trp-Phe (WF) finger into the membrane. Molecular dynamics simulations show that WIPIs and the WF finger cooperatively stabilize the complex on membranes. Biochemical reconstitution and cell-based assays show that WIPI3:ATG13 engagement promotes ATG16L1 phosphorylation, autophagy, and mitophagy. A kinase domain (KD)-proximal Pro-Val-Pro (PVP) motif in the ULK1 intrinsically disordered region docks onto the ATG13:ATG101 HORMA dimer brings the ULK1 KD close to the membrane. The PVP motif is essential for in vitro ULK1 phosphorylation of ATG16L1 and important for autophagy and mitophagy. These data establish a stepwise pathway for recruitment of the ULK1 KD to the vicinity of the membrane surface.

Indexed as

AutophagyAutophagy-Related Protein-1 HomologCell MembraneIntracellular Signaling Peptides and ProteinsAdaptor Proteins, Signal TransducingAutophagy-Related ProteinsHumansMembrane ProteinsMolecular Dynamics SimulationPhosphatidylinositol PhosphatesPhosphorylationProtein BindingVesicular Transport ProteinsAdaptor Proteins, Signal TransducingATG101 protein, humanATG13 protein, humanAutophagy-Related Protein-1 HomologAutophagy-Related ProteinsIntracellular Signaling Peptides and ProteinsMembrane ProteinsPhosphatidylinositol PhosphatesULK1 protein, humanVesicular Transport Proteins

Identifiers

PMID42696573
PMCPMC13544240

What OpenQuestion holds

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Registered trials

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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.