APP Deletion Accounts for Age-Dependent Changes in the Bioenergetic Metabolism and in Hyperphosphorylated CaMKII at Stimulated Hippocampal Presynaptic Active Zones
| Autor: | Walter Volknandt, Ulrike Müller, Ina Koch, Benedikt Beckert, Martin Wegner, Amparo Acker-Palmer, Jens Weingarten, Eva Harde, Michael Karas, Moritz Neupärtl, Jörg Ackermann, Vahid Golghalyani, Melanie Laßek, Tabiwang N. Array |
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| Přispěvatelé: | Tempia, Filippo |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
hippocampus Hyperphosphorylation amyloid precursor protein Biology Hippocampal formation Synaptic vesicle 03 medical and health sciences Cellular and Molecular Neuroscience Ca2+/calmodulin-dependent protein kinase ddc:570 mental disorders Amyloid precursor protein Original Research aging Long-term potentiation Cell Biology presynaptic active zone Synaptic vesicle cycle mitochondria 030104 developmental biology biology.protein LTP Neuroscience Presynaptic active zone |
| Zdroj: | Frontiers in Synaptic Neuroscience Front. Synaptic Neurosci. |
| ISSN: | 1663-3563 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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