Table 3. Three separate mechanisms act concurrently to shed and release PrPC from the PrP-expressing cell culture system used in this study.
Mechanism of release | PrP fragment | Time course of released PrPwt | Time course of released PrPΔ121–123 | Suggested compartment | Proposed enzymatic activity | Inhibition or hindering |
---|---|---|---|---|---|---|
α-cleavage |
N1 (11 kDa) |
20 min |
20 min (rate inhibited by 45%) |
Cell membrane |
Putative α-PrPase |
Deletions in the site for α-cleavage |
Extreme C-terminal cleavage |
FL-S C1-S |
40–60 min |
40–60 min |
Endocytic compartment |
Metallo-protease(s) |
O-phenanthroline, TAPI-1 |
Exosomal release | FL C1 |
5–6 h | 5–6 h | MVBs | N/A | - |
N/A, not applicable.