The trans-Golgi network is a major site for -secretase processing of amyloid precursor protein in primary neurons

Abstract

Amyloid precursor protein (APP) is processed along the amyloidogenic pathway by the -secretase, BACE1, generating -amyloid (A), or along the nonamyloidogenic pathway by -secretase, precluding A production. The plasma membrane is considered the major site for -secretase–mediated APP cleavage, but other cellular locations have not been rigorously investigated. Here, we report that APP is processed by endogenous -secretase at the trans-Golgi network (TGN) of both transfected HeLa cells and mouse primary neurons. We have previously shown the adaptor protein complex, AP-4, and small G protein ADP-ribosylation factor–like GTPase 5b (Arl5b) are required for efficient post-Golgi transport of APP to ..