Phosphoproteomic Alterations of Ionotropic Glutamate Receptors in the Hippocampus of the Ts65Dn Mouse Model of Down Syndrome

Frontiers in Molecular Neuroscience
Macarena Gómez de SalazarXavier Altafaj

Abstract

Down syndrome (DS), the main genetic cause of intellectual disability, is associated with an imbalance of excitatory/inhibitory neurotransmitter systems. The phenotypic assessment and pharmacotherapy interventions in DS murine models strongly pointed out glutamatergic neurotransmission alterations (specially affecting ionotropic glutamate receptors [iGluRs]) that might contribute to DS pathophysiology, which is in agreement with DS condition. iGluRs play a critical role in fast-mediated excitatory transmission, a process underlying synaptic plasticity. Neuronal plasticity is biochemically modulated by post-translational modifications, allowing rapid and reversible adaptation of synaptic strength. Among these modifications, phosphorylation/dephosphorylation processes strongly dictate iGluR protein-protein interactions, cell surface trafficking, and subsynaptic mobility. Hence, we hypothesized that dysregulation of phosphorylation/dephosphorylation balance might affect neuronal function, which in turn could contribute to the glutamatergic neurotransmitter alterations observed in DS. To address this point, we biochemically purified subsynaptic hippocampal fractions from adult Ts65Dn mice, a trisomic mouse model recapitulating DS p...Continue Reading

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Citations

May 29, 2020·The European Journal of Neuroscience·Xavier L WarnetMagnus Kjaergaard

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Methods Mentioned

BETA
acetylation
electron microscopy
transgenic

Software Mentioned

Proteome Discoverer
STRING
GraphPad
Mascot
Image Lab Biorad
Phosphomotif Finder
VENNY
Search Tool for the

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