Understanding the role of tetraspanins as modulators of the metalloprotease ADAM10
With about 100 membrane protein as substrates, the metalloprotease ADisintegrin And Metalloprotease 10 (ADAM10) is important for physiological processes in the brain and other organs. These substrates include the Amyloid Precursor Protein (APP), the cellular Prion Protein (PrPc) and the neuronal cadherin (N-cadherin). ADAM10-mediated ectodomain shedding is regulated by tetraspanins, small four transmembrane spanning proteins that modulate the trafficking, maturation and half-life of the protease. A member of the TspanC6 subfamily, Tspan 3, regulates ADAM10-mediated shedding and acts as a scaffold protein stabilizing ADAM10 at the cell-surface. Tspan 7, as an additional TspanC6 member has been discussed to interact with ADAM10. Moreover, the TspanC8 subfamily (Tspan 5, Tspan 10, Tspan 14, Tspan 15, Tspan 17, and Tspan 33) regulate ADAM10 maturation and surface trafficking. This study is based on the hypothesis that selected ADAM10-modulating tetraspanins act in concert and can replace for each other. Therefore, in this study the modulatory role of the TspanC6 members Tspan 3 and Tspan 7, and the TspanC8 members Tspan 5, Tspan 14 and Tspan 15 on ADAM10 were characterized in more detail.
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