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Biosynthesis and differential processing of two pools of amyloid‐β precursor protein in a physiologically inducible neuroendocrine cell
Author(s) -
Collin Rob W. J.,
Van Den Hurk Wilhelmina H.,
Martens Gerard J. M.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03243.x
Subject(s) - amyloid precursor protein , intracellular , biology , microbiology and biotechnology , xenopus , biosynthesis , neuroendocrine cell , context (archaeology) , alpha secretase , biochemistry , p3 peptide , proteolysis , secretory pathway , cell , alzheimer's disease , enzyme , medicine , gene , golgi apparatus , immunology , disease , paleontology , immunohistochemistry
The amyloid‐β precursor protein (APP) is linked to Alzheimer's disease through its pathological proteolytic processing in the secretory pathway. Nevertheless, surprisingly little is known about the biosynthesis of endogenous APP. We therefore decided to investigate the intracellular fate of newly synthesized APP in a physiologically inducible neuroendocrine cell, the Xenopus intermediate pituitary melanotrope cell. We found that the level of both APP mRNA and protein was about threefold induced in the activated cells of black‐adapted animals. Intriguingly, two pools of APP were found, only one of which was up‐regulated. This induced pool became readily N ‐ and subsequently O ‐glycosylated and was eventually proteolytically processed by an α‐secretase‐like cleavage event resulting in a secreted N‐terminal and a cell‐associated C‐terminal APP fragment. Conversely, only the other (non‐induced, non‐glycosylated and uncleaved) pool became phosphorylated. Thus, we report on the biosynthesis of APP in a physiological context and illuminate the occurrence of two pools of APP, one of which is linked to neuroendocrine cell activation.