title: Pulse-chase experiments revealed beta-secretase cleavage from immature full-length amyloid precursor protein harboring the Swedish mutation. Implications for distinct pathways.
abstract: The molecular mechanisms of the nonamyloidogenic and the amyloidogenic pathways of the amyloid precursor protein (APP) are unknown, but proteolysis of APP is essential for the generation of beta-amyloid. To study the time-course of C-terminal fragment generation by alpha- and beta-secretase, we expressed the APP751 isoform with the Swedish mutation in the human neuroblastoma cell line SY5Y as previously described (Urmoneit et al., 1995). We show in pulse-chase experiments that the C-terminal fragments, CT, generated by alpha-secretase and A4CT, generated by beta-secretase, could be generated from immature full-length APP before O-glycosylation is completed. Thus beta A4 may be generated from immature APP that has not passed through the trans-Golgi-network (TGN), which presents experimental evidence for the intracellular localization of beta-secretase activity in an earlier Golgi complex.
authors: University of Düsseldorf, Berlin, Germany.
authors: B
authors: B
authors: Urmoneit
authors: J
authors: J
authors: Turner
authors: T
authors: T
authors: Dyrks
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases; D020126:Brefeldin A / Q000494:pharmacology; D002451:Cell Compartmentation / Q000502:physiology; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism / Q000494:pharmacology; D008985:Monensin / Q000494:pharmacology; D016296:Mutagenesis / Q000502:physiology; D009447:Neuroblastoma; D010446:Peptide Fragments / Q000378:metabolism; D010957:Plasmids; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013462:Sulfur Radioisotopes; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
chemical_list: D016564:Amyloid beta-Protein Precursor; D007476:Ionophores; D010446:Peptide Fragments; D011500:Protein Synthesis Inhibitors; D013462:Sulfur Radioisotopes; D020126:Brefeldin A; D008985:Monensin; D008715:Methionine; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human