Truncated PrP(c) in mammalian brain: interspecies variation and location in membrane rafts.

A key molecular event in prion diseases is the conversion of cellular prion protein (PrP(c)) into an abnormal misfolded conformer (PrP(sc)). The PrP(c) N-terminal domain plays a central role in PrP(c) functions and in prion propagation. Because mammalian PrP(c) is found as a full-length and N-terminally truncated form, we examined the presence and amount of PrP(c) C-terminal fragment in the brain of different species. We found important variations between primates and rodents. In addition, our data show that the PrP(c) fragment is present in detergent-resistant raft domains, a membrane domain of critical importance for PrP(c) functions and its conversion into PrP(sc)

The N-terminal cleavage of cellular prion protein in the human brain

AbstractHuman brain cellular prion protein (PrPc) is cleaved within its highly conserved domain at amino acid 110/111↓112. This cleavage generates a highly stable C-terminal fragment (C1). We examined the relative abundance of holo- and truncated PrPc in human cerebral cortex and we found important inter-individual variations in the proportion of C1. Neither age nor postmortem interval explain the large variability observed in C1 amount. Interestingly, our results show that high levels of C1 are associated with the presence of the active ADAM10 suggesting this zinc metalloprotease as a candidate for the cleavage of PrPc in the human brain