Endogenous C-terminal fragments of beta-amyloid precursor protein from Xenopus laevis skin exudate

Abstract Using a monoclonal antibody against the entire C-terminal end of human APP 695 (643–695 sequence) and a monoclonal antibody directed against human β [1–40] amyloid peptide ( β A), we show the existence of endogenous peptides proteolytically derived from APP in skin exudate of the non transgenic Xenopus laevis frog. The majority of the immunoreactivity is found associated with a 30 kDa molecular species. Biochemical fractionation followed by mass spectrometry identification allowed us to assign this molecular species to C-terminal APP fragments containing all or part of β A. According to the nature of N- and C-terminal amino acids we identified endogenous β -, γ -, e -secretase-like activities, caspase-like activity and numerous endogenous cleavage sites within the β -amyloid sequence at same sites as those observed in human β A sequence. All these homologies with human indicate that X . laevis skin exudate is a good natural model to study β A metabolism. In this way, interestingly, we identified endogenous cleavages at prohormone convertase-like sites not yet described at the same sites in human. Finally, all identified peptide fragments were stably associated with a 20.2 kDa protein. These new observed features suggest new research pathways concerning human β A metabolism and carriage of hydrophobic peptide fragments issued from APP processing.