Figure 3

Distinctly regulated β-amyloid precursor protein and β-site β-amyloid precursor protein cleaving enzyme 1 trafficking. β-Amyloid precursor protein (APP) and β-site APP cleaving enzyme 1 (BACE1) trafficking is differentially regulated from the site of trans-Golgi network exit, internalization and further sorting into different compartments. Internalization of APP occurs through recruitment of the adaptor-protein complex AP-2 and Dab2 for clathrin-mediated endocytosis. Munc18-interacting protein (Mint; also called X11) is involved in the outward transport of APP from the trans-Golgi network to the plasma membrane. The recycling pathway of BACE1 is mediated by Golgi-localized γ-ear-containing ARF-binding proteins (GGAs). ADP-ribosylation factor-6 (ARF6) mediates sorting of newly internalized BACE1 into Rab5-positive early endosome and GGA3 could modulate BACE1 turnover and stability while sorting it into the lysosome.