Figure 6.
APP cleavage by the meprin heterodimer. A) Diagram of APP cleavage by cell surface–bound meprin β and impaired cleavage by soluble meprins. Cleavage of cell surface–bound meprin β and subsequent γ-secretase cleavage leads to generation of accumulating Aβ fragments in the extracellular space. Catalytically inactive meprin β E153A was used for the meprin enzyme complex to exclude meprin β cleavage. B) Transfection of HeLa cells with APP, meprin WT, or meprin β E153A variant. Immunoblotting of cell lysates and supernatants revealed cleavage of APP and Aβ generation by active meprin β, not by membrane-bound meprin α or inactive meprin β. Recombinant Aβ served as positive control. Mep, meprin; N-, N terminus; rec., recombinant.