The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex
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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 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 09:33
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Projects: Published Datasets, Unpublished Datasets
Institutions: LMU Klinikum
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Projects: Published Datasets, Unpublished Datasets
Institutions: DZNE
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Public web page: Not specified
Submitter: Rainer Malik
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Assays: Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Bottom-up proteomics (human), Bottom-up proteomics (mouse), Bottom-up proteomics (mouse), Bottom-up proteomics (mouse), Bottom-up proteomics (mouse), Gel-based experiment (human), Phosphoproteomics / Bottom-up proteomics (mouse), Proximity-proteomics-based autophagosome content profiling (human), SWATH MS (human), SWATH MS (human, mouse), SWATH MS (mouse), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human, mouse), Shotgun proteomics (human, mouse), Shotgun proteomics (human, mouse), Shotgun proteomics (human, mouse), Shotgun proteomics (macaque), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (rat), Untargeted Proteomics (mouse)
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: Proteomics
Technology type: Technology Type
Investigation: Proteomics (Published)
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 ...
Creators: None
Submitter: Rainer Malik
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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
