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Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points
Synaptic integrity and function depend on myriad proteins - labile molecules with finite lifetimes that need to be continually replaced with freshly synthesized copies. Here we describe experiments designed to expose synaptic (and neuronal) properties and functions that are particularly sensitive to...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9792512/ https://www.ncbi.nlm.nih.gov/pubmed/36583084 http://dx.doi.org/10.3389/fnmol.2022.1038614 |
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author | Cohen, Laurie D. Ziv, Tamar Ziv, Noam E. |
author_facet | Cohen, Laurie D. Ziv, Tamar Ziv, Noam E. |
author_sort | Cohen, Laurie D. |
collection | PubMed |
description | Synaptic integrity and function depend on myriad proteins - labile molecules with finite lifetimes that need to be continually replaced with freshly synthesized copies. Here we describe experiments designed to expose synaptic (and neuronal) properties and functions that are particularly sensitive to disruptions in protein supply, identify proteins lost early upon such disruptions, and uncover potential, yet currently underappreciated failure points. We report here that acute suppressions of protein synthesis are followed within hours by reductions in spontaneous network activity levels, impaired oxidative phosphorylation and mitochondrial function, and, importantly, destabilization and loss of both excitatory and inhibitory postsynaptic specializations. Conversely, gross impairments in presynaptic vesicle recycling occur over longer time scales (days), as does overt cell death. Proteomic analysis identified groups of potentially essential ‘early-lost’ proteins including regulators of synapse stability, proteins related to bioenergetics, fatty acid and lipid metabolism, and, unexpectedly, numerous proteins involved in Alzheimer’s disease pathology and amyloid beta processing. Collectively, these findings point to neuronal excitability, energy supply and synaptic stability as early-occurring failure points under conditions of compromised supply of newly synthesized protein copies. |
format | Online Article Text |
id | pubmed-9792512 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97925122022-12-28 Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points Cohen, Laurie D. Ziv, Tamar Ziv, Noam E. Front Mol Neurosci Molecular Neuroscience Synaptic integrity and function depend on myriad proteins - labile molecules with finite lifetimes that need to be continually replaced with freshly synthesized copies. Here we describe experiments designed to expose synaptic (and neuronal) properties and functions that are particularly sensitive to disruptions in protein supply, identify proteins lost early upon such disruptions, and uncover potential, yet currently underappreciated failure points. We report here that acute suppressions of protein synthesis are followed within hours by reductions in spontaneous network activity levels, impaired oxidative phosphorylation and mitochondrial function, and, importantly, destabilization and loss of both excitatory and inhibitory postsynaptic specializations. Conversely, gross impairments in presynaptic vesicle recycling occur over longer time scales (days), as does overt cell death. Proteomic analysis identified groups of potentially essential ‘early-lost’ proteins including regulators of synapse stability, proteins related to bioenergetics, fatty acid and lipid metabolism, and, unexpectedly, numerous proteins involved in Alzheimer’s disease pathology and amyloid beta processing. Collectively, these findings point to neuronal excitability, energy supply and synaptic stability as early-occurring failure points under conditions of compromised supply of newly synthesized protein copies. Frontiers Media S.A. 2022-12-13 /pmc/articles/PMC9792512/ /pubmed/36583084 http://dx.doi.org/10.3389/fnmol.2022.1038614 Text en Copyright © 2022 Cohen, Ziv and Ziv. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) 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. |
spellingShingle | Molecular Neuroscience Cohen, Laurie D. Ziv, Tamar Ziv, Noam E. Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points |
title | Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points |
title_full | Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points |
title_fullStr | Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points |
title_full_unstemmed | Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points |
title_short | Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points |
title_sort | synapse integrity and function: dependence on protein synthesis and identification of potential failure points |
topic | Molecular Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9792512/ https://www.ncbi.nlm.nih.gov/pubmed/36583084 http://dx.doi.org/10.3389/fnmol.2022.1038614 |
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