Autor: |
Alexandra L. Matthews, Stefan F. Lichtenthaler, Edward T Davis, Hung-En Hsia, Antonia Malinova, Alessandro Di Maio, Michael G. Tomlinson, Justyna Szyroka, Paul Saftig, Michael C. Sykes, Neale Harrison, Katie Willis, Philip R. Morrison, Eleanor Cull, Chek Ziu Koo, Eric Rubinstein, Clara Apicella, Joelle Goulding, Stephen J. Briddon, Murat Keles, Lisa Seipold, Nicholas D. Holliday, Stephan A. Mueller, Bethany Cragoe, Natalie S. Poulter, Thomas A. McFarlane, Haroon Ahmed, Peter J. Noy, Johanna Tüshaus |
Rok vydání: |
2019 |
Předmět: |
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Popis: |
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 to what degree 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 intimate ADAM10/TspanC8 scissor complex. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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