Ubiquitin and Alzheimer's amyloid beta precursor protein colocalize to endosomes-lysosomes in cultured human cells.
Chloroquine (CHQ)-sensitive cellular compartments, identified as endosomes-lysosomes (ELs), have been implicated in the proteolysis of amyloid 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). Immunoblotting analysis of cell lysates indicated a significant degree of CHQ-mediated interference in A beta PP metabolism in a time- and concentration-dependent manner. The implication is that abnormal intracellular accumulation of A beta PP and its C-terminal fragments beyond a certain threshold may trigger the Ub response. We hypothesize that Ub may play a role in A beta PP processing and/or trafficking to ELs, particularly in stress-related conditions.
Ali-Khan
Z
Z
Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
Chan
S L
SL
Jung
S S
SS
Chronopoloulos
S
S
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D009447:Neuroblastoma / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D014452:Ubiquitins