Evidence map›Paper›PMID 31932738›Full record

ArticleNature cell biology2020

The LC3-conjugation machinery specifies the loading of RNA-binding proteins into extracellular vesicles.

Andrew M Leidal, Hector H Huang, Timothy Marsh, Tina Solvik, Dachuan Zhang, Jordan Ye, FuiBoon Kai, Juliet Goldsmith, Jennifer Y Liu, Yu-Hsin Huang and 7 more

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 340 papers.

0numbers the graph read from it
0cells of the map it votes in
340citing papers in PubMed
24.6field-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

340 citing papers in PubMed, 463 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 2 countries.

Andrew M LeidalDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Hector H HuangDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0908-9008
Timothy MarshDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-8772-7645
Tina SolvikDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Dachuan ZhangState Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Jordan YeDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
FuiBoon KaiDepartment of Surgery, University of California San Francisco, San Francisco, CA, USA.
Juliet GoldsmithDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Jennifer Y LiuDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Yu-Hsin HuangDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Teresa MonkkonenDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Ariadne VlahakisDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Eric J HuangDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-5381-3801
Hani GoodarziDepartment of Biochemistry and Biophysics, Department of Urology, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9648-8949
Li YuState Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Arun P WiitaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7465-6964
Jayanta DebnathDepartment of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. Jayanta.Debnath@ucsf.edu.ORCID http://orcid.org/0000-0002-8745-4069
University of California, San Francisco · USPeking University · CN

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
UCSF IRACDA Scholars ProgramK12GM081266 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Raymond M. Esquerra, HOLLY A. INGRAHAM · 2007 to 2026
$19.4M
Molecular and Cellular Mechanisms in CancerT32CA108462 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2004 to 2024
$10.4M
Endolysosomal defects in secretory autophagy and microglial toxicity in FTDR01AG057462 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jayanta Debnath, Eric J Huang · 2017 to 2026
$6.9M
Autophagy in Adhesion and MetastasisR01CA126792 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jayanta Debnath · 2009 to 2026
$5.3M
An antisense RNA-mediated regulatory program that drives cancer metastasisR01CA240984 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOODARZI, HANI · 2019 to 2023
$2.5M
Autophagy as a microenvironmental regulator of tumorigenesis and resistanceR01CA188404 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BERGERS, GABRIELE, DEBNATH, JAYANTA · 2014 to 2018
$2.1M
Targeted regulation of transcript stability through RNA methylation and intron retentionR01GM123977 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOODARZI, HANI · 2017 to 2021
$2.0M
Stromal Fibroblast Autophagy In Tumor Progression and DesmoplasiaR01CA213775 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DEBNATH, JAYANTA · 2018 to 2022
$1.9M
Exploiting myeloma proteome remodeling to extend proteasome inhibitor efficacyR01CA226851 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WIITA, ARUN P. · 2018 to 2022
$1.6M
Systematic dissection of an aberrant splicing program driving cancer metastasisR00CA194077 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOODARZI, HANI · 2016 to 2018
$746k
Global Assessment of Myeloma Response to ChemotherapyK08CA184116 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WIITA, ARUN P. · 2014 to 2018
$684k
NCI NIH HHS F30 CA224693NCI NIH HHS F31 CA217015NCI NIH HHS K08 CA184116NCI NIH HHS R00 CA194077NCI NIH HHS R01 CA126792NCI NIH HHS R01 CA188404NCI NIH HHS R01 CA213775NCI NIH HHS R01 CA226851NCI NIH HHS R01 CA240984NCI NIH HHS R21 CA201849NCI NIH HHS T32 CA108462NIA NIH HHS R01 AG057462NIGMS NIH HHS K12 GM081266NIGMS NIH HHS R01 GM123977NIGMS NIH HHS T32 GM007618
6 · The paper itself

Abstract

Traditionally viewed as an autodigestive pathway, autophagy also facilitates cellular secretion; however, the mechanisms underlying these processes remain unclear. Here, we demonstrate that components of the autophagy machinery specify secretion within extracellular vesicles (EVs). Using a proximity-dependent biotinylation proteomics strategy, we identify 200 putative targets of LC3-dependent secretion. This secretome consists of a highly interconnected network enriched in RNA-binding proteins (RBPs) and EV cargoes. Proteomic and RNA profiling of EVs identifies diverse RBPs and small non-coding RNAs requiring the LC3-conjugation machinery for packaging and secretion. Focusing on two RBPs, heterogeneous nuclear ribonucleoprotein K (HNRNPK) and scaffold-attachment factor B (SAFB), we demonstrate that these proteins interact with LC3 and are secreted within EVs enriched with lipidated LC3. Furthermore, their secretion requires the LC3-conjugation machinery, neutral sphingomyelinase 2 (nSMase2) and LC3-dependent recruitment of factor associated with nSMase2 activity (FAN). Hence, the LC3-conjugation pathway controls EV cargo loading and secretion.

Indexed as

Adaptor Proteins, Vesicular TransportAnimalsAutophagosomesAutophagyAutophagy-Related Protein 7Autophagy-Related ProteinsBiological TransportBiotinylationExtracellular VesiclesGene Expression ProfilingGene Expression RegulationHEK293 CellsHeterogeneous-Nuclear Ribonucleoprotein KHumansIntracellular Signaling Peptides and ProteinsLysosomesAdaptor Proteins, Vesicular TransportATG14 protein, humanATG7 protein, humanAutophagy-Related Protein 7Autophagy-Related ProteinsHeterogeneous-Nuclear Ribonucleoprotein KHNRNPK protein, humanIntracellular Signaling Peptides and ProteinsMAP1LC3A protein, humanMatrix Attachment Region Binding ProteinsMicrotubule-Associated ProteinsNSMAF protein, humanNuclear Matrix-Associated ProteinsReceptors, EstrogenRNA-Binding ProteinsRNA, Small UntranslatedSAFB protein, humanSMPD3 protein, humanSphingomyelin Phosphodiesterase

Identifiers

PMID31932738
PMCPMC7007875
OpenAlexW3000522739

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.