Society for Neuroscience Annual Meeting: Another APP Secretase?
Just when it appeared as though the mechanisms of the proteolytic processing of APP were finally becoming apparent, Andreas Weidemann presented an elegant study demonstrating the existence of a different processing event (122.2). Using SH5Y and Cos-7 cells expressing C-terminally tagged APP and SPACT (C99) he isolated C-terminal fragments (CTFs) from membrane preparations and by radiosequencing demonstrated the presence of a CTF generated by cleavage between Leu645 and Val646 (APP695 numbering). Cleavage at this site (termed epsilon) appeared to occur late in the secretory pathway and was not affected by γ-secretase inhibitors and did not appear to be a precursor to γ-secretase cleavage.—Dominic Walsh
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