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Conversely, treatments with methylamine or colchicine had no significant effect on the secretion of total APP. Treatment of these cells with the lysosomotropic amine chloroquine resulted in a significant increase in the levels of both cell surface full\u2010length APP and cell surface\u2010derived secreted nexin II (NXII). Immunofluorescence analysis of C6 glioma cells transfected with APP<jats:sub>751<\/jats:sub> indicated that under normal conditions, cell surface APP was internalized, and within 30 minutes was localized in discrete intracellular vesicles. These vesicles contained the endocytic tracer Texas red\u2010conjugated ovalbumin and probably represented late endosomes or lyso\u2010somes. However, treatment of the transfected C6 cultures with methylamine or colchicine prevented localization of cell surface APP in intracellular vesicles, suggesting that these treatments altered the normal intracellular trafficking of cell surface\u2010derived APP. Both the biochemical and immunofluorescence data are compatible with the suggestion that inhibition of normal endocytic internalization reduces the secretory cleavage of cell surface APP. Furthermore, our results suggest that following internalization, cell surface APP is cleaved by secretase(s) and secreted or routed to the lysosomes where it is degraded. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.490400515","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T02:07:22Z","timestamp":1104545242000},"page":"694-706","source":"Crossref","is-referenced-by-count":50,"title":["Evidence that secretase cleavage of cell surface Alzheimer amyloid precursor occurs after normal endocytic internalization"],"prefix":"10.1002","volume":"40","author":[{"given":"L. 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