Evidence map›Paper›PMID 32111735›Full record

ArticleThe Journal of biological chemistry2020

The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex.

Chek Ziu Koo, Neale Harrison, Peter J Noy, Justyna Szyroka, Alexandra L Matthews, Hung-En Hsia, Stephan A Müller, Johanna Tüshaus, Joelle Goulding, Katie Willis and 21 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.4field-weighted citation impact, top 4% 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

30 citing papers in PubMed, 43 citations in OpenAlex.

  1. Assessing genetic risk factors for early-onset coronary artery disease in Iranians.Research and practice in thrombosis and haemostasis · 2026
    Article
  2. Lipid-Facilitated Opening of the ADAM10 Sheddase Revealed by Enhanced Sampling Simulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Tetraspanin TSP-12 and SUP-17/ADAM10 exhibit cell type-specific codependence for trafficking through the Golgi.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  18. Molecular Mechanisms of Hemostasis, Thrombosis and Thrombo-Inflammation.International journal of molecular sciences · 2022
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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

31 authors at 6 institutions in 3 countries.

Chek Ziu KooSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.ORCID 0000-0003-3770-2594
Neale HarrisonSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.ORCID 0000-0001-6821-4089
Peter J NoySchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Justyna SzyrokaSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Alexandra L MatthewsSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Hung-En HsiaGerman Center for Neurodegenerative Diseases (DZNE) Munich, Neuroproteomics, Klinikum rechts der Isar, Technical University Munich and Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
Stephan A MüllerGerman Center for Neurodegenerative Diseases (DZNE) Munich, Neuroproteomics, Klinikum rechts der Isar, Technical University Munich and Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.ORCID 0000-0003-3414-307X
Johanna TüshausGerman Center for Neurodegenerative Diseases (DZNE) Munich, Neuroproteomics, Klinikum rechts der Isar, Technical University Munich and Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
Joelle GouldingCentre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Midlands B15 2TT, United Kingdom.ORCID 0000-0002-6227-4483
Katie WillisSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Clara ApicellaSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Bethany CragoeSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Edward DavisSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Murat KelesSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Antonia MalinovaSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Thomas A McFarlaneSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Philip R MorrisonSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Hanh T H NguyenSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Michael C SykesSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Haroon AhmedSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Alessandro Di MaioSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Lisa SeipoldInstitute of Biochemistry, Christian Albrechts University Kiel, 24118 Kiel, Germany.
Paul SaftigInstitute of Biochemistry, Christian Albrechts University Kiel, 24118 Kiel, Germany.
Eleanor CullSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.ORCID 0000-0002-4309-4858
Christos PliotasSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.
Eric RubinsteinSorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris 75013, France.
Natalie S PoulterCentre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Midlands B15 2TT, United Kingdom.ORCID 0000-0002-3187-2130
Stephen J BriddonCentre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Midlands B15 2TT, United Kingdom.
Nicholas D HollidayDivision of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, United Kingdom.
Stefan F LichtenthalerGerman Center for Neurodegenerative Diseases (DZNE) Munich, Neuroproteomics, Klinikum rechts der Isar, Technical University Munich and Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
Michael G TomlinsonSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom m.g.tomlinson@bham.ac.uk.ORCID 0000-0002-1189-0091
University of Birmingham · GBGerman Center for Neurodegenerative Diseases · DEUniversity of Nottingham · GBChristian-Albrechts-Universität zu Kiel · DECentre National de la Recherche Scientifique · FRUniversity of Leeds · GB

Funding

Biotechnology and Biological Sciences Research Council BB/P00783X/1British Heart Foundation FS/18/9/33388British Heart Foundation PG/13/92/30587
6 · The paper itself

Abstract

A disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein essential for embryonic development, and its dysregulation underlies disorders such as cancer, Alzheimer's disease, and inflammation. ADAM10 is a "molecular scissor" that proteolytically cleaves the extracellular region from >100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors, and chemokines. ADAM10 has been recently proposed to function as six distinct scissors with different substrates, depending on its association with one of six regulatory tetraspanins, termed TspanC8s. However, it remains unclear to what degree ADAM10 function critically depends on a TspanC8 partner, and a lack of monoclonal antibodies specific for most TspanC8s has hindered investigation of this question. To address this knowledge gap, here we designed an immunogen to generate the first monoclonal antibodies targeting Tspan15, a model TspanC8. The immunogen was created in an ADAM10-knockout mouse cell line stably overexpressing human Tspan15, because we hypothesized that expression in this cell line would expose epitopes that are normally blocked by ADAM10. Following immunization of mice, this immunogen strategy generated four Tspan15 antibodies. Using these antibodies, we show that endogenous Tspan15 and ADAM10 co-localize on the cell surface, that ADAM10 is the principal Tspan15-interacting protein, that endogenous Tspan15 expression requires ADAM10 in cell lines and primary cells, and that a synthetic ADAM10/Tspan15 fusion protein is a functional scissor. Furthermore, two of the four antibodies impaired ADAM10/Tspan15 activity. These findings suggest that Tspan15 directly interacts with ADAM10 in a functional scissor complex.

Indexed as

A549 CellsADAM10 ProteinAmyloid Precursor Protein SecretasesAnimalsHEK293 CellsHumansJurkat CellsMembrane ProteinsMiceMice, KnockoutMultiprotein ComplexesTetraspaninsADAM10 ProteinADAM10 protein, humanAdam10 protein, mouseAmyloid Precursor Protein SecretasesMembrane ProteinsMultiprotein ComplexesTetraspaninsTSPAN15 protein, humanADAMADAM10a disintegrin and metalloproteasemembrane proteinmetalloproteinasemolecular cell biologymonoclonal antibodysheddingtetraspaninTspan14Tspan15

Identifiers

PMID32111735
PMCPMC7476718
OpenAlexW3008776068

What OpenQuestion holds

Textmetadata
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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.