Evidence map›Paper›PMID 29339438›Full record

ArticleThe Journal of cell biology2018

Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling.

Frederik Johannes Verweij, Maarten P Bebelman, Connie R Jimenez, Juan J Garcia-Vallejo, Hans Janssen, Jacques Neefjes, Jaco C Knol, Richard de Goeij-de Haas, Sander R Piersma, S Rubina Baglio and 11 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in The Journal of cell biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 217 papers.

0numbers the graph read from it
0cells of the map it votes in
217citing papers in PubMed
11.3field-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

217 citing papers in PubMed, 357 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 9 institutions in 3 countries.

Frederik Johannes VerweijDepartment of Pathology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands frederik.verweij@curie.fr.ORCID 0000-0001-8879-1174
Maarten P BebelmanDepartment of Pathology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands.ORCID 0000-0003-4007-5093
Connie R JimenezDepartment of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
Juan J Garcia-VallejoDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands.
Hans JanssenDivision of Cell Biology, Netherlands Cancer Institute, Amsterdam, Netherlands.ORCID 0000-0001-7480-793X
Jacques NeefjesDepartment of Chemical Immunology, Leiden University Medical Center, Leiden, Netherlands.
Jaco C KnolDepartment of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
Richard de Goeij-de HaasDepartment of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
Sander R PiersmaDepartment of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
S Rubina BaglioDepartment of Pathology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
Matthijs VerhageDepartment of Clinical Genetics, VU University Medical Center, Amsterdam, Netherlands.
Jaap M MiddeldorpDepartment of Pathology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands.ORCID 0000-0002-0765-4125
Anoek ZomerCancer Genomics Netherlands-Hubrecht Institute-Koninklijke Nederlandse Akademie van Wetenschappen, Utrecht, Netherlands.
Jacco van RheenenCancer Genomics Netherlands-Hubrecht Institute-Koninklijke Nederlandse Akademie van Wetenschappen, Utrecht, Netherlands.
Marc G CoppolinoDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, Canada.
Ilse HurbainInstitut Curie, Paris Sciences et Lettres Research University, Centre National de la Recherché Scientifique, UMR 144, Paris, France.ORCID 0000-0002-0097-7773
Graça RaposoInstitut Curie, Paris Sciences et Lettres Research University, Centre National de la Recherché Scientifique, UMR 144, Paris, France.
Martine J SmitDivision of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems, VU University Amsterdam, Amsterdam, Netherlands.
Ruud F G ToonenDepartment of Clinical Genetics, VU University Medical Center, Amsterdam, Netherlands.ORCID 0000-0002-9900-4233
Guillaume van NielInstitut Curie, Paris Sciences et Lettres Research University, Centre National de la Recherché Scientifique, UMR 144, Paris, France.ORCID 0000-0002-8651-9705
D Michiel PegtelDepartment of Pathology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, Netherlands d.pegtel@vumc.nl.ORCID 0000-0002-7357-4406
Amsterdam UMC Location Vrije Universiteit Amsterdam · NLCentre National de la Recherche Scientifique · FRAmsterdam Neuroscience · NLRoyal Netherlands Academy of Arts and Sciences · NLVrije Universiteit Amsterdam · NLBiologie cellulaire et Cancer · FRLeiden University Medical Center · NLThe Netherlands Cancer Institute · NLUniversity of Guelph · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Exosomes are small endosome-derived extracellular vesicles implicated in cell-cell communication and are secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology are based on isolation procedures after secretion, precluding direct and dynamic insight into the mechanics of exosome biogenesis and the regulation of their release. In this study, we propose real-time visualization of MVB-PM fusion to overcome these limitations. We designed tetraspanin-based pH-sensitive optical reporters that detect MVB-PM fusion using live total internal reflection fluorescence and dynamic correlative light-electron microscopy. Quantitative analysis demonstrates that MVB-PM fusion frequency is reduced by depleting the target membrane SNAREs SNAP23 and syntaxin-4 but also can be induced in single cells by stimulation of the histamine H1 receptor (H1HR). Interestingly, activation of H1R1 in HeLa cells increases Ser110 phosphorylation of SNAP23, promoting MVB-PM fusion and the release of CD63-enriched exosomes. Using this single-cell resolution approach, we highlight the modulatory dynamics of MVB exocytosis that will help to increase our understanding of exosome physiology and identify druggable targets in exosome-associated pathologies.

Indexed as

Cell CommunicationCell MembraneExocytosisHCT116 CellsHeLa CellsHistamineHumansHuman Umbilical Vein Endothelial CellsMembrane FusionMultivesicular BodiesPhosphorylationPotassium ChlorideQa-SNARE ProteinsQb-SNARE ProteinsQc-SNARE ProteinsReceptors, G-Protein-CoupledHistaminePotassium ChlorideQa-SNARE ProteinsQb-SNARE ProteinsQc-SNARE ProteinsReceptors, G-Protein-CoupledReceptors, Histamine H1SNAP23 protein, humansyntaxin 4, humanTetraspaninsTSPAN1 protein, human

Identifiers

PMID29339438
PMCPMC5839777
OpenAlexW2783004471

What OpenQuestion holds

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LicenceCC BY
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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.