Molecular architecture of postsynaptic Interactomes

Cell Signal. 2020 Dec:76:109782. doi: 10.1016/j.cellsig.2020.109782. Epub 2020 Sep 14.

Abstract

The postsynaptic density (PSD) plays an essential role in the organization of the synaptic signaling machinery. It contains a set of core scaffolding proteins that provide the backbone to PSD protein-protein interaction networks (PINs). These core scaffolding proteins can be seen as three principal layers classified by protein family, with DLG proteins being at the top, SHANKs along the bottom, and DLGAPs connecting the two layers. Early studies utilizing yeast two hybrid enabled the identification of direct protein-protein interactions (PPIs) within the multiple layers of scaffolding proteins. More recently, mass-spectrometry has allowed the characterization of whole interactomes within the PSD. This expansion of knowledge has further solidified the centrality of core scaffolding family members within synaptic PINs and provided context for their role in neuronal development and synaptic function. Here, we discuss the scaffolding machinery of the PSD, their essential functions in the organization of synaptic PINs, along with their relationship to neuronal processes found to be impaired in complex brain disorders.

Keywords: Interactomes; Postsynaptic density, PSD; Protein interaction networks; Scaffolds; Synaptic signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Line
  • Humans
  • Membrane Proteins / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Post-Synaptic Density / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Synapses / metabolism*

Substances

  • Membrane Proteins
  • Nerve Tissue Proteins