Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders

Nat Neurosci. 2017 Aug;20(8):1150-1161. doi: 10.1038/nn.4594. Epub 2017 Jun 26.


The postsynaptic density (PSD) contains a collection of scaffold proteins used for assembling synaptic signaling complexes. However, it is not known how the core-scaffold machinery associates in protein-interaction networks or how proteins encoded by genes involved in complex brain disorders are distributed through spatiotemporal protein complexes. Here using immunopurification, proteomics and bioinformatics, we isolated 2,876 proteins across 41 in vivo interactomes and determined their protein domain composition, correlation to gene expression levels and developmental integration to the PSD. We defined clusters for enrichment of schizophrenia, autism spectrum disorders, developmental delay and intellectual disability risk factors at embryonic day 14 and adult PSD in mice. Mutations in highly connected nodes alter protein-protein interactions modulating macromolecular complexes enriched in disease risk candidates. These results were integrated into a software platform, Synaptic Protein/Pathways Resource (SyPPRes), enabling the prioritization of disease risk factors and their placement within synaptic protein interaction networks.

MeSH terms

  • Animals
  • Brain Diseases / genetics
  • Brain Diseases / metabolism
  • Disease Models, Animal
  • Guanylate Kinases / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics*
  • Post-Synaptic Density / genetics*
  • Schizophrenia / genetics
  • Schizophrenia / metabolism
  • Signal Transduction / genetics
  • Synapses / genetics
  • Synapses / metabolism*


  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Guanylate Kinases