APP deletion accounts for age-dependent changes in the bioenergetic metabolism and in hyperphosphorylated CaMKII at stimulated hippocampal presynaptic active zones

Synaptic release sites are characterized by exocytosis-competent synaptic vesicles tightly anchored to the presynaptic active zone (PAZ) whose proteome orchestrates the fast signaling events involved in synaptic vesicle 
Synaptic release sites are characterized by exocytosis-competent synaptic vesicles tightly anchored to the presynaptic active zone (PAZ) whose proteome orchestrates the fast signaling events involved in synaptic vesicle cycle and plasticity. Allocation of the amyloid precursor protein (APP) to the PAZ proteome implicated a functional impact of APP in neuronal communication. In this study, we combined state-of-the-art proteomics, electrophysiology and bioinformatics to address protein abundance and functional changes at the native hippocampal PAZ in young and old APP-KO mice. We evaluated if APP deletion has an impact on the metabolic activity of presynaptic mitochondria. Furthermore, we quantified differences in the phosphorylation status after long-term-potentiation (LTP) induction at the purified native PAZ. We observed an increase in the phosphorylation of the signaling enzyme calmodulin-dependent kinase II (CaMKII) only in old APP-KO mice. During aging APP deletion is accompanied by a severe decrease in metabolic activity and hyperphosphorylation of CaMKII. This attributes an essential functional role to APP at hippocampal PAZ and putative molecular mechanisms underlying the age-dependent impairments in learning and memory in APP-KO mice.
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Metadaten
Author:Melanie Laßek, Jens Weingarten, Martin Wegner, Moritz Neupärtl, Tabiwang N. Array, Eva Harde, Benedikt Beckert, Vahid Golghalyani, Jörg Ackermann, Ina Koch, Ulrike C. Müller, Michael Karas, Amparo Acker-Palmer, Walter Volknandt
URN:urn:nbn:de:hebis:30:3-451568
DOI:http://dx.doi.org/10.3389/fnsyn.2017.00001
ISSN:1663-3563
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28163681
Parent Title (English):Frontiers in synaptic neuroscience
Publisher:Frontiers Research Foundation
Place of publication:Lausanne
Contributor(s):Filippo Tempia
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/01/20
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/12/05
Tag:LTP; aging; amyloid precursor protein; hippocampus; mitochondria; presynaptic active zone
Volume:9
Issue:Art. 1
Pagenumber:14
First Page:1
Last Page:14
Note:
Copyright © 2017 Laßek, Weingarten, Wegner, Neupärtl, Array, Harde, Beckert, Golghalyani, Ackermann, Koch, Müller, Karas, Acker-Palmer and Volknandt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
HeBIS PPN:427942594
Institutes:Pharmazie
Biowissenschaften
Informatik
Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Biowissenschaften
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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