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  • Title: Pulse-chase experiments revealed beta-secretase cleavage from immature full-length amyloid precursor protein harboring the Swedish mutation. Implications for distinct pathways.
    Author: Urmoneit B, Turner J, Dyrks T.
    Journal: J Mol Neurosci; 1998 Oct; 11(2):141-50. PubMed ID: 10096041.
    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.
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