Distinct anterograde trafficking pathways of BACE1 and amyloid precursor protein from the TGN and the regulation of amyloid-beta production

Abstract

Processing of amyloid precursor protein (APP) by the β-secretase BACE1 is the initial step of the amyloidogenic pathway to generate amyloid-β (Aβ). Although newly synthesized BACE1 and APP are transported along the secretory pathway, it is not known whether BACE1 and APP share the same post-Golgi trafficking pathways or are partitioned into different transport routes. Here we demonstrate that BACE1 exits the Golgi in HeLa cells and primary neurons by a pathway distinct from the trafficking pathway for APP. By using the Retention Using Selective Hooks system, we show that BACE1 is transported from the trans-Golgi network to the plasma membrane in an AP-1- and Arf1/4-dependent manner. Subseque..