Proteomic analysis of postsynaptic proteins in regions of the human neocortex.
Marcia RoyOksana SorokinaNathan SkeneClémence SimonnetFrancesca MazzoRuud ZwartEmanuele SherColin SmithJ Douglas ArmstrongSeth G N GrantPublished in: Nature neuroscience (2017)
The postsynaptic proteome of excitatory synapses comprises ~1,000 highly conserved proteins that control the behavioral repertoire, and mutations disrupting their function cause >130 brain diseases. Here, we document the composition of postsynaptic proteomes in human neocortical regions and integrate it with genetic, functional and structural magnetic resonance imaging, positron emission tomography imaging, and behavioral data. Neocortical regions show signatures of expression of individual proteins, protein complexes, biochemical and metabolic pathways. We characterized the compositional signatures in brain regions involved with language, emotion and memory functions. Integrating large-scale GWAS with regional proteome data identifies the same cortical region for smoking behavior as found with fMRI data. The neocortical postsynaptic proteome data resource can be used to link genetics to brain imaging and behavior, and to study the role of postsynaptic proteins in localization of brain functions.
Keyphrases
- resting state
- functional connectivity
- positron emission tomography
- electronic health record
- white matter
- magnetic resonance imaging
- computed tomography
- genome wide
- endothelial cells
- big data
- high resolution
- autism spectrum disorder
- cerebral ischemia
- magnetic resonance
- depressive symptoms
- binding protein
- dna methylation
- working memory
- induced pluripotent stem cells
- transcription factor
- pluripotent stem cells
- multiple sclerosis
- smoking cessation
- gene expression
- subarachnoid hemorrhage
- copy number
- mass spectrometry
- fluorescence imaging
- artificial intelligence
- diffusion weighted imaging