Document Detail


Biosynthesis and differential processing of two pools of amyloid-beta precursor protein in a physiologically inducible neuroendocrine cell.
MedLine Citation:
PMID:  16092943     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rob W J Collin; Wilhelmina H van den Hurk; Gerard J M Martens
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  94     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-08-11     Completed Date:  2005-09-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1015-24     Citation Subset:  IM    
Affiliation:
Department of Molecular Animal Physiology, Nijmegen Center for Molecular Life Sciences and Institute for Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological
Amyloid beta-Protein Precursor / biosynthesis,  genetics,  metabolism*
Animals
Color
Glycosylation
Melanocyte-Stimulating Hormones / secretion
Peptide Hydrolases / metabolism
Phosphorylation
Pituitary Gland / cytology,  metabolism*
Protein Processing, Post-Translational*
RNA, Messenger / metabolism
Xenopus laevis
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein Precursor; 0/RNA, Messenger; 9002-79-3/Melanocyte-Stimulating Hormones; EC 3.4.-/Peptide Hydrolases

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