Evidence map›Paper›PMID 31758005›Full record

ArticleScientific reports2019

Membrane-bound Gaussia luciferase as a tool to track shedding of membrane proteins from the surface of extracellular vesicles.

Mikołaj Piotr Zaborowski, Pike See Cheah, Xuan Zhang, Isabella Bushko, Kyungheon Lee, Alessandro Sammarco, Valentina Zappulli, Sybren Lein Nikola Maas, Ryan M Allen, Purva Rumde and 9 more

Abstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Tracking human neurologic disease status in mouse brain/plasma using reporter-tagged, EV-associated biomarkers.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  5. Engineered EVs designed to target diseases of the CNS.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Exosome-based liquid biopsies in cancer: opportunities and challenges.Annals of oncology : official journal of the European Society for Medical Oncology · 2021
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
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

19 authors.

Mikołaj Piotr ZaborowskiDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA. mikolaj.zaborowski@gmail.com.ORCID http://orcid.org/0000-0002-4400-6688
Pike See CheahDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Xuan ZhangDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Isabella BushkoDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Kyungheon LeeCenter for Systems Biology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Alessandro SammarcoDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.ORCID http://orcid.org/0000-0003-1977-3292
Valentina ZappulliDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Sybren Lein Nikola MaasDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Ryan M AllenDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Purva RumdeDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Bence GyörgyDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Massimo AufieroDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Markus W SchweigerDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.ORCID http://orcid.org/0000-0002-8197-3044
Charles Pin-Kuang LaiDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Ralph WeisslederCenter for Systems Biology, Massachusetts General Hospital, Boston, MA, 02114, USA.ORCID http://orcid.org/0000-0003-0828-4143
Hakho LeeCenter for Systems Biology, Massachusetts General Hospital, Boston, MA, 02114, USA.ORCID http://orcid.org/0000-0002-0087-0909
Kasey C VickersDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Bakhos A TannousDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Xandra O BreakefieldDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, 02129, USA. breakefield@hms.harvard.edu.

Funding

The role of microvesicles in giloma virotherapyP01CA069246 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHAREST, ALAIN · 1996 to 2021
$30.9M
Non-coding RNA & Bioinformatics CoreP01HL116263 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DAVIES, SEAN STEPHEN · 2014 to 2025
$24.7M
Interdepartmental Neuroscience CenterP30NS045776 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS, TANNOUS, BAKHOS A · 2003 to 2018
$11.1M
Transfer of microRNA regulators from glioblastoma to brain microenvironment U19CA179563 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS, CHAREST, ALAIN · 2013 to 2017
$8.6M
The power of extracellular vesicles in glioblastomaR35CA232103 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS · 2018 to 2024
$6.9M
Early Detection through Novel OCEAN Technology - Ovarian Cancer Exosomal Analysis with NanoplasmonicsU01CA233360 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CASTRO, CESAR M, DINULESCU, DANIELA M · 2018 to 2022
$3.5M
Clinical platform for high-throughput analyses of extracellular vesiclesR01CA229777 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI LEE, HAKHO, SKOG, JOHAN · 2018 to 2022
$3.2M
HDL-microRNA Intercellular Communication in AtherosclerosisR01HL128996 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI VICKERS, KASEY C · 2015 to 2019
$2.3M
Macrophage SR-BI Regulates Autophagy, Angiogenin and tRNA-derived small RNAsR01HL127173 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LINTON, MACRAE F, VICKERS, KASEY C · 2016 to 2019
$2.1M
NCI NIH HHS P01 CA069246NCI NIH HHS R01 CA229777NCI NIH HHS R35 CA232103NCI NIH HHS U01 CA233360NCI NIH HHS U19 CA179563NHLBI NIH HHS P01 HL116263NHLBI NIH HHS R01 HL127173NHLBI NIH HHS R01 HL128996NINDS NIH HHS P30 NS045776
6 · The paper itself

Abstract

Extracellular vesicles (EVs) released by cells play a role in intercellular communication. Reporter and targeting proteins can be modified and exposed on the surface of EVs to investigate their half-life and biodistribution. A characterization of membrane-bound Gaussia luciferase (mbGluc) revealed that its signal was detected also in a form smaller than common EVs (<70 nm). We demonstrated that mbGluc initially exposed on the surface of EVs, likely undergoes proteolytic cleavage and processed fragments of the protein are released into the extracellular space in active form. Based on this observation, we developed a new assay to quantitatively track shedding of membrane proteins from the surface of EVs. We used this assay to show that ectodomain shedding in EVs is continuous and is mediated by specific proteases, e.g. metalloproteinases. Here, we present a novel tool to study membrane protein cleavage and release using both in vitro and in vivo models.

Indexed as

AnimalsCell Line, TumorCopepodaExtracellular VesiclesFemaleHumansLuciferasesMembrane ProteinsMembranesMiceMice, NudeRecombinant ProteinsSecretory PathwayTissue DistributionLuciferasesMembrane ProteinsRecombinant Proteins

Identifiers

PMID31758005
PMCPMC6874653

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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.