Proteolytic cleavage of PrPC. After cleavage of the N-terminal and GPI anchor signal peptides (grey), mature membrane-bound PrPC can undergo at least three different proteolytic cleavage events (scissors) in addition to phospholipase C cutting within its GPI anchor. While β-cleavage is mainly observed under pathological conditions, a role of ADAM10 is discussed in the context of both, constitutive α-cleavage and shedding of PrPC. The resulting fragments are shown underneath. Striped box: octameric repeat region; checked box: hydrophobic core domain. Epitopes of PrPC specific monoclonal antibodies POM1 and POM2 used in this study are indicated.