A disintegrin and metalloprotease 10 (ADAM10) is essential for embryonic development and impacts on diseases such as cancer, Alzheimer’s and inflammatory diseases. ADAM10 is a ‘molecular scissor’ that proteolytically cleaves the extracellular region from over 100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors and chemokines. ADAM10 was 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 whether ADAM10 function is critically dependent on a TspanC8 partner. To address this, we generated the first monoclonal antibodies to Tspan15 as a model TspanC8. These were used to show that ADAM10 is the principal Tspan15-interacting protein, that Tspan15 expression requires ADAM10 in cell lines and primary cells, and that a synthetic ADAM10/Tspan15 fusion protein is a functional scissor. Together these findings suggest that ADAM10 exists as an ADAM10/TspanC8 scissor complex.
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Created: 8th Jul 2024 at 09:35
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Version 1 (earliest) Created 8th Jul 2024 at 09:35 by Rainer Malik
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Projects: SyNergy - published datasets
Institutions: DZNE
Projects: SyNergy - published datasets
Institutions: Klinikum der Universität München
Projects: SyNergy - published datasets
Institutions: DZNE
Public web page: Not specified
Organisms: Mus musculus, Rattus norvegicus, Homo sapiens, Macaca mulatta, Sus scrofa
Submitter: Rainer Malik
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A disintegrin and metalloprotease 10 (ADAM10) is essential for embryonic development and impacts on diseases such as cancer, Alzheimer’s and inflammatory diseases. ADAM10 is a ‘molecular scissor’ that proteolytically cleaves the extracellular region from over 100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors and chemokines. ADAM10 was recently proposed to function as six distinct scissors with different substrates, depending on its association with one of six ...
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2 x 108 wild-type or Tspan15-knockout HEK-293T cells were lysed in 1% digitonin lysis buffer containing protease inhibitor cocktail (Sigma-Aldrich). Lysates were pre-cleared with protein G sepharose prior to immunoprecipitation with Tspan15 mAb 1C12 chemically cross-linked to protein G sepharose with dimethyl pimelimidate (Thermo Fisher Scientific). Five independent immunoprecipitations were carried out for each cell type. Immunoprecipitation samples in non-reducing Laemmli buffer were subjected ...
Submitter: Rainer Malik
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Proteomics
Organisms: Homo sapiens
SOPs: No SOPs
Data files: Tetraspanin Tspan15 is an essential subunit of ...
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Abstract (Expand)
Authors: C. Z. Koo, N. Harrison, P. J. Noy, J. Szyroka, A. L. Matthews, H. E. Hsia, S. A. Muller, J. Tushaus, J. Goulding, K. Willis, C. Apicella, B. Cragoe, E. Davis, M. Keles, A. Malinova, T. A. McFarlane, P. R. Morrison, H. T. H. Nguyen, M. C. Sykes, H. Ahmed, A. Di Maio, L. Seipold, P. Saftig, E. Cull, C. Pliotas, E. Rubinstein, N. S. Poulter, S. J. Briddon, N. D. Holliday, S. F. Lichtenthaler, M. G. Tomlinson
Date Published: 4th Sep 2020
Publication Type: Journal
PubMed ID: 32111735
Citation: J Biol Chem. 2020 Sep 4;295(36):12822-12839. doi: 10.1074/jbc.RA120.012601. Epub 2020 Feb 28.