The beta-amyloid precursor protein is not processed by the regulated secretory pathway.
The beta-amyloid peptide is derived from a larger membrane bound protein and accumulates as amyloid in Alzheimer's diseased brains. beta-amyloid precursor protein (beta APP) proteolytically processed during constitutive secretion cannot be a source of deposited amyloid because this processing results in cleavage within the amyloidogenic peptide. To see if other secretory pathways could be responsible for generating potentially amyloidogenic molecules we tested the possibility that beta APP is targeted to the regulated secretory pathway. Stable AtT20 cell lines expressing exogenous human beta APP were genetically engineered. These cells were labeled with [35S]-methionine, and chased in the presence or absence of secretagogue. The beta APP both inside the cells and released from the cells was analyzed by immunoprecipitation and gel analysis. Quantitation of autoradiograms showed that virtually all of the synthesized beta APP was secreted by the constitutive pathway, and that no detectable (less than 1%) beta APP was targeted to the regulated secretory pathway.
Overly
C C
CC
Athena Neurosciences, Inc., South San Francisco, CA 94080.
Fritz
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LC
Lieberburg
I
I
McConlogue
L
L
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000235:genetics; D006801:Humans; D007163:Immunosorbent Techniques; D007700:Kinetics; D051379:Mice; D010902:Pituitary Gland / Q000378:metabolism; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D004247:DNA