Evidence map›Paper›PMID 41278708›Full record

ArticlebioRxiv : the preprint server for biology2025

Reconstitution of multistep recruitment of ULK1 to membranes in autophagy.

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

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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.
Ye LuDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Sanjoy PaulAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
Johannes BetzDepartment of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
Lea WilhelmAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
Annan S I CookDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Xuefeng RenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Elias AdriaenssensAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
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.
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 ULK1 complex (ULK1C) and the class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) act together to initiate autophagy. Human ULK1C consists of ULK1 itself, FIP200, and the HORMA domain heterodimer ATG13:ATG101. PI3P generated by PI3KC3-C1 is essential to recruit and stabilize ULK1C on membranes for ULK1 to phosphorylate its membrane-associated substrates in autophagy induction, even though ULK1C subunits do not contain any PI3P-binding domains. Here we show that the ATG13:ATG101 dimer forms a tight complex with the PI3P-binding protein WIPI3, as well as with WIPI2. Bound to WIPI2-3, ATG13:ATG101 aligns with the membrane to insert its Trp-Phe (WF) finger into the membrane. Molecular dynamics simulations show that alignment of WIPIs and the ATG101 WF finger cooperatively stabilizes the complex on membranes, explaining the essential role of the WF residues in autophagy. Biochemical reconstitution and a cell-based assay show that WIPI3:ATG13 engagement is required for ATG16L1 phosphorylation by ULK1, ATG13 puncta formation, and bulk autophagic flux. We further showed that a kinase domain (KD)-proximal PVP motif within the ULK1 IDR docks onto the surface of the ATG13:ATG101 HORMA dimer and used molecular modeling to show how the ULK1 KD is brought close to the membrane surface. Biochemical reconstitution and cell-based assays show that the PVP motif is essential for

Identifiers

PMID41278708
PMCPMC12637519

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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.