Protease inhibitors divert amyloid precursor protein to the secretory pathway.
Addition of cysteine protease inhibitors to cells expressing amyloid precursor protein (APP) resulted in a >2-fold increase in appearance of the secreted extracellular domain of APP in the media. This was accounted for by increased flux of APP into the secretory pathway since protease inhibitors also caused a twofold increase in newly translated, incompletely glycosylated APP detected by pulse-labeling. These results show that a portion of newly translated APP molecules are normally rapidly degraded by cysteine protease(s) but can enter the secretory pathway when degradation is inhibited. Newly translated APP molecules are thus still competent for posttranslational processing in distal cellular compartments. Their degradation thus may not result from misfolding but merely susceptibility to an endoplasmic reticulum localized cysteine protease.
Hare
J F
JF
Department of Biochemistry, Oregon Health Sciences University, Portland, Oregon 97219, USA. hare@ohsu.edu
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D015853:Cysteine Proteinase Inhibitors; D008565:Membrane Proteins; D009842:Oligopeptides; C408403:acetyl-leucyl-leucyl-normethional; C069861:calpain inhibitor 2