Evidence map›Paper›PMID 26038556›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

GABARAPs regulate PI4P-dependent autophagosome:lysosome fusion.

Hanzhi Wang, Hui-Qiao Sun, Xiaohui Zhu, Li Zhang, Joseph Albanesi, Beth Levine, Helen Yin

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 2 pooled it
11.1field-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

121 citing papers in PubMed, 2 syntheses or guidelines pooled it, 213 citations in OpenAlex.

  1. Guideline
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  3. Review
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  5. Article
  6. The Role of Sigmar1 in Autophagy Regulation and Disease Therapy.International journal of molecular sciences · 2026
    Review
  7. Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026
    Review
  8. Article
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  12. Review
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  18. Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025
    Review
  19. Article
  20. Article

61 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

7 authors at 2 institutions in 3 countries.

Hanzhi WangDepartment of Physiology.
Hui-Qiao SunDepartment of Physiology.
Xiaohui ZhuDepartment of Physiology.
Li ZhangDepartment of Physiology.
Joseph AlbanesiDepartment of Pharmacology.
Beth LevineDepartment of Internal Medicine, Center for Autophagy Research, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390 Beth.Levine@utsouthwestern.edu Helen.Yin@UTSouthwestern.edu.
Helen YinDepartment of Physiology, Beth.Levine@utsouthwestern.edu Helen.Yin@UTSouthwestern.edu.
Czech Academy of Sciences, Institute of Physiology · CZSouthwestern Medical Center · US

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7M
Novel epigenetic mechanisms in neuronal development and cognitive functionR01MH096066 · NIMH · BOSTON CHILDREN'S HOSPITAL · PI ARLOTTA, PAOLA, POMEROY, SCOTT LOREN · 2012 to 2022
$6.1M
Histone Demethylases and Regulation of Chromatin and Transcription in EukaryotesR01CA118487 · NCI · HARVARD MEDICAL SCHOOL · PI SHI, YANG · 2006 to 2017
$3.6M
ANALYSIS OF BECLIN 1 IN AUTOPHAGY AND TUMOR SUPPRESSIONR01CA084254 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI LEVINE, BETH C · 2000 to 2009
$3.5M
Beclin 1-Bcl-2 Interactions: Effects on AutophagyR01CA109618 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI LEVINE, BETH C · 2004 to 2014
$3.1M
Phosphoinsitide Regulation of the GolgiR01GM066110 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI YIN, HELEN L · 2004 to 2011
$3.0M
NCI NIH HHS CA118487NCI NIH HHS P30 CA142543NCI NIH HHS R01 CA084254NCI NIH HHS R01 CA109618NIGMS NIH HHS R01 GM066110NIMH NIH HHS MH096066
6 · The paper itself

Abstract

The Atg8 autophagy proteins are essential for autophagosome biogenesis and maturation. The γ-aminobutyric acid receptor-associated protein (GABARAP) Atg8 family is much less understood than the LC3 Atg8 family, and the relationship between the GABARAPs' previously identified roles as modulators of transmembrane protein trafficking and autophagy is not known. Here we report that GABARAPs recruit palmitoylated PI4KIIα, a lipid kinase that generates phosphatidylinositol 4-phosphate (PI4P) and binds GABARAPs, from the perinuclear Golgi region to autophagosomes to generate PI4P in situ. Depletion of either GABARAP or PI4KIIα, or overexpression of a dominant-negative kinase-dead PI4KIIα mutant, decreases autophagy flux by blocking autophagsome:lysosome fusion, resulting in the accumulation of abnormally large autophagosomes. The autophagosome defects are rescued by overexpressing PI4KIIα or by restoring intracellular PI4P through "PI4P shuttling." Importantly, PI4KIIα's role in autophagy is distinct from that of PI4KIIIβ and is independent of subsequent phosphatidylinositol 4,5 biphosphate (PIP2) generation. Thus, GABARAPs recruit PI4KIIα to autophagosomes, and PI4P generation on autophagosomes is critically important for fusion with lysosomes. Our results establish that PI4KIIα and PI4P are essential effectors of the GABARAP interactome's fusion machinery.

Indexed as

Cell FusionAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsHeLa CellsHumansImmunoprecipitationLysosomesMicroscopy, ConfocalMicroscopy, ElectronMicrotubule-Associated ProteinsMinor Histocompatibility AntigensPhagosomesPhosphatidylinositol PhosphatesPhosphotransferases (Alcohol Group Acceptor)RNA, Small InterferingAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsGABARAP protein, humanMicrotubule-Associated ProteinsMinor Histocompatibility Antigensphosphatidylinositol 4-phosphatephosphatidylinositol phosphate 4-kinasePhosphatidylinositol PhosphatesPhosphotransferases (Alcohol Group Acceptor)RNA, Small Interferingautophagosome:lysosome fusionautophagyGABARAPPI4KIIαPI4P

Identifiers

PMID26038556
PMCPMC4460452
OpenAlexW1583543179

What OpenQuestion holds

Textmetadata
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.