Unbiased proteomic analysis of postsynaptic density fractions from Shank3 mutant mice reveals brain region specific changes highly relevant to autism spectrum disorder

ABSTRACT: Disruption of the human SHANK3 gene can cause several neuropsychiatric disease entities including Phelan-McDermid syndrome (PMS), autism spectrum disorders (ASDs) and intellectual disability (ID). Although a wide array of neurobiological studies strongly supports a major role for SHANK3 in organizing the postsynaptic protein scaffold, the molecular processes at synapses of individuals harboring SHANK3 mutations are still far from being understood. In this study, we biochemically isolated the postsynaptic density (PSD) fraction from striatum and hippocampus of Shank3Δ11-/- mutant mice and performed ion-mobility enhanced data-independent label-free LC-MS/MS to obtain the corresponding PSD proteomes. This unbiased approach to identify molecular disturbances at PSDs devoid of major Shank3 isoforms revealed largely distinct molecular alterations in striatum and hippocampus. Being the first comprehensive analysis of brain region specific PSD proteomes from a Shank3 mutant line, our study provides crucial information on molecular alterations that could foster translational treatment studies for SHANK3 mutation-associated synaptopathies and possibly also ASD in general.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Ute Distler  

LAB HEAD: Stefan Tenzer

PROVIDER: PXD005192 | Pride | 2017-03-08

REPOSITORIES: Pride