Long-term potentiation modulates synaptic phosphorylation networks and reshapes the structure of the postsynaptic interactome.
Sci Signal
; 9(440): rs8, 2016 08 09.
Article
em En
| MEDLINE
| ID: mdl-27507650
ABSTRACT
The postsynaptic site of neurons is composed of more than 1500 proteins arranged in protein-protein interaction complexes, the composition of which is modulated by protein phosphorylation through the actions of complex signaling networks. Components of these networks function as key regulators of synaptic plasticity, in particular hippocampal long-term potentiation (LTP). The postsynaptic density (PSD) is a complex multicomponent structure that includes receptors, enzymes, scaffold proteins, and structural proteins. We triggered LTP in the mouse hippocampus CA1 region and then performed large-scale analyses to identify phosphorylation-mediated events in the PSD and changes in the protein-protein interactome of the PSD that were associated with LTP induction. Our data indicated LTP-induced reorganization of the PSD. The dynamic reorganization of the PSD links glutamate receptor signaling to kinases (writers) and phosphatases (erasers), as well as the target proteins that are modulated by protein phosphorylation and the proteins that recognize the phosphorylation status of their binding partners (readers). Protein phosphorylation and protein interaction networks converged at highly connected nodes within the PSD network. Furthermore, the LTP-regulated phosphoproteins, which included the scaffold proteins Shank3, Syngap1, Dlgap1, and Dlg4, represented the "PSD risk" for schizophrenia and autism spectrum disorder, such that without these proteins in the analysis, the association with the PSD and these two psychiatric diseases was not present. These data are a rich resource for future studies of LTP and suggest that the PSD holds the keys to understanding the molecular events that contribute to complex neurological disorders that affect synaptic plasticity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Proteínas Quinases
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Sinapses
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Transdução de Sinais
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Potenciação de Longa Duração
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Fosfoproteínas Fosfatases
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Região CA1 Hipocampal
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article