Evidence map›Paper›PMID 30933966›Full record

ArticlePLoS biology2019

CRISPR screening using an expanded toolkit of autophagy reporters identifies TMEM41B as a novel autophagy factor.

Christopher J Shoemaker, Tina Q Huang, Nicholas R Weir, Nicole J Polyakov, Sebastian W Schultz, Vladimir Denic

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 1 pooled it
14.2field-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

97 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.

  1. Guideline
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  5. Article
  6. Core principles of autophagy initiation mechanisms.Nature structural & molecular biology · 2026
    Review
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  15. The Proteomic Analysis of Intermittent Fasting Alone or with GLP-1RA in NAFLD Rats.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025
    Article
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  17. Article
  18. Review
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37 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

6 authors at 2 institutions in 2 countries.

Christopher J ShoemakerDepartment of Molecular and Cellular Biology, Harvard University, Northwest Labs, Cambridge, Massachusetts, United States of America.
Tina Q HuangDepartment of Molecular and Cellular Biology, Harvard University, Northwest Labs, Cambridge, Massachusetts, United States of America.
Nicholas R WeirDepartment of Molecular and Cellular Biology, Harvard University, Northwest Labs, Cambridge, Massachusetts, United States of America.
Nicole J PolyakovDepartment of Molecular and Cellular Biology, Harvard University, Northwest Labs, Cambridge, Massachusetts, United States of America.
Sebastian W SchultzCentre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway.
Vladimir DenicDepartment of Molecular and Cellular Biology, Harvard University, Northwest Labs, Cambridge, Massachusetts, United States of America.ORCID 0000-0002-1982-7281
Harvard University · USOslo University Hospital · NO

Funding

Understanding the role of RNA-binding protein mutations in cancerP20GM113132 · NIGMS · DARTMOUTH COLLEGE · PI MIERKE, DALE F · 2016 to 2025
$25.9M
Mechanistic dissection of eukaryotic protein biogenesis and degradation pathwaysR35GM127136 · NIGMS · HARVARD UNIVERSITY · PI Vladimir Denic · 2018 to 2026
$5.0M
Elucidating the function of mammalian autophagy receptors in selective autophagyR00GM117218 · NIGMS · DARTMOUTH COLLEGE · PI SHOEMAKER, CHRISTOPHER J · 2019 to 2021
$747k
Elucidating the function of mammalian autophagy receptors in selective autophagyK99GM117218 · NIGMS · HARVARD UNIVERSITY · PI SHOEMAKER, CHRISTOPHER J · 2016 to 2017
$180k
NIGMS NIH HHS K99 GM117218NIGMS NIH HHS P20 GM113132NIGMS NIH HHS R00 GM117218NIGMS NIH HHS R35 GM127136
6 · The paper itself

Abstract

The power of forward genetics in yeast is the foundation on which the field of autophagy research firmly stands. Complementary work on autophagy in higher eukaryotes has revealed both the deep conservation of this process, as well as novel mechanisms by which autophagy is regulated in the context of development, immunity, and neuronal homeostasis. The recent emergence of new clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-based technologies has begun facilitating efforts to define novel autophagy factors and pathways by forward genetic screening in mammalian cells. Here, we set out to develop an expanded toolkit of autophagy reporters amenable to CRISPR/Cas9 screening. Genome-wide screening of our reporters in mammalian cells recovered virtually all known autophagy-related (ATG) factors as well as previously uncharacterized factors, including vacuolar protein sorting 37 homolog A (VPS37A), transmembrane protein 251 (TMEM251), amyotrophic lateral sclerosis 2 (ALS2), and TMEM41B. To validate this data set, we used quantitative microscopy and biochemical analyses to show that 1 novel hit, TMEM41B, is required for phagophore maturation. TMEM41B is an integral endoplasmic reticulum (ER) membrane protein distantly related to the established autophagy factor vacuole membrane protein 1 (VMP1), and our data show that these two factors play related, albeit not fully overlapping, roles in autophagosome biogenesis. In sum, our work uncovers new ATG factors, reveals a malleable network of autophagy receptor genetic interactions, and provides a valuable resource (http://crispr.deniclab.com) for further mining of novel autophagy mechanisms.

Indexed as

AutophagyCRISPR-Cas SystemsEndoplasmic ReticulumHumansK562 CellsMembrane ProteinsProtein TransportMembrane ProteinsTMEM41B protein, humanVMP1 protein, human

Identifiers

PMID30933966
PMCPMC6459555
OpenAlexW2933052407

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.