Biosynthesis and differential processing of two pools of amyloid-beta precursor protein in a physiologically inducible neuroendocrine cell.
The amyloid-beta 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 alpha-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.
Collin
Rob W J
RW
Department of Molecular Animal Physiology, Nijmegen Center for Molecular Life Sciences and Institute for Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands.
van den Hurk
Wilhelmina H
WH
Martens
Gerard J M
GJ
D000222:Adaptation, Physiological; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003116:Color; D006031:Glycosylation; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D014982:Xenopus laevis
D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D009074:Melanocyte-Stimulating Hormones; D010447:Peptide Hydrolases