Secretory Carrier Membrane Protein 3’s (SCAMP3) Role in β-amyloid Production and Secretion

Abstract:

Alzheimer’s disease is a neurodegenerative disease associated with loss of memory and cognitive function. The aggregation of extracellular plaques containing β-amyloid is related to the processing of the amyloid precursor protein (APP). When endocytosed to the early endosome, APP will either be degraded by the lysosome or sent back to the trans-Golgi network. Degradation of APP is regulated by endosomal sorting complexes required for transport (ESCRTs). Disruption of ESCRT function leads to accumulation of β-amyloid. The secretory carrier membrane protein 3 (SCAMP3) interacts and opposes the function of the ESCRT proteins. In this study, we have found that expression of APP-EGFP in H4 neuroglioma colocalizes with SCAMP3. Interestingly, APP-EGFP and SCAMP3 are found in the trans-Golgi Network in transiently transfected cells and in the late endosome/lysosome in stably transfected cells. These results suggest that SCAMP3 has a role in regulating APP trafficking in the TGN-endolysosomal system. We hypothesize then that SCAMP3 may regulate APP trafficking by promoting or inhibiting trafficking of APP to the lysosome and propose to examine SCAMP’s effects using RNA interference in both an immunofluorescence and biochemical ELISA assays.