UBIQUITIN AND ALZHEIMERS AMYLOID-BETA PRECURSOR PROTEIN COLOCALIZE TOENDOSOMES-LYSOSOMES IN CULTURED HUMAN-CELLS

CHLOROQUINE (CHQ)-sensitive cellular compartments, identified as endos omes-lysosomes (ELs), have been implicated in the proteolysis of amylo id beta precursor protein (A beta PP) in Alzheimer's disease. Here we show using immunocytochemistry and immunogold electron microscopy that not only A beta PP but also ubiquitin (Ub) co-localize to ELs in CHQ- treated human neuroblastoma (SK-N-SH) and glioblastoma (U-373). Immuno blotting analysis of cell lysates indicated a significant degree of CH Q-mediated interference in A beta PP metabolism in a time- and concent ration-dependent manner. The implication is that abnormal intracellula r accumulation of A beta PP and its C-terminal fragments beyond a cert ain threshold may trigger the Ub response. We hypothesize that Ub may play a role in A beta PP processing and/or trafficking to ELs, particu larly in stress-related conditions.