BACE2 is localized to intracellular compartments relevant to Aß degradation. A, Exogenous administration of fluorescently labeled Aß40 (green) to CHO cells results in accumulation at intracellular sites overlapping with lysosomes, as labelled by Lysotracker Red (red) and visualized by confocal microscopy. B, BACE2 is expressed in multiple intracellular compartments, including lysosomes. Distribution of GFP-tagged BACE2 (green) in cells labeled with Lysotracker Red (red) shows significant localization within lysosomes (yellow). C, BACE2 colocalizes with exogenously administered Aß. Confocal images showing significant overlap (yellow) between BACE2 (green) and fluorescently labeled Aß (red). For these experiments, cells were imaged within 5 minutes of washing in cold PBS to remove medium containing excess fluorescently labeled Aß. Note that the the majority of BACE2-GFP-expressing cells contianed very low levels of fluorescent Aß (see Figure 7), and the particular cell shown exhibited relatively high levels of internalized Aß, allowing us to highlight the overlap with BACE2.