MPP2 is a postsynaptic MAGUK scaffold protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density

Sci Rep. 2016 Oct 19;6:35283. doi: 10.1038/srep35283.

Abstract

At neuronal synapses, multiprotein complexes of trans-synaptic adhesion molecules, scaffold proteins and neurotransmitter receptors assemble to essential building blocks required for synapse formation and maintenance. Here we describe a novel role for the membrane-associated guanylate kinase (MAGUK) protein MPP2 (MAGUK p55 subfamily member 2) at synapses of rat central neurons. Through interactions mediated by its C-terminal SH3-GK domain module, MPP2 binds to the abundant postsynaptic scaffold proteins PSD-95 and GKAP and localises to postsynaptic sites in hippocampal neurons. MPP2 also colocalises with the synaptic adhesion molecule SynCAM1. We demonstrate that the SynCAM1 C-terminus interacts directly with the MPP2 PDZ domain and that MPP2 does not interact in this manner with other highly abundant postsynaptic transmembrane proteins. Our results highlight a previously unexplored role for MPP2 at postsynaptic sites as a scaffold that links SynCAM1 cell adhesion molecules to core proteins of the postsynaptic density.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Disks Large Homolog 4 Protein / genetics
  • Disks Large Homolog 4 Protein / metabolism
  • Hippocampus / metabolism
  • Immunoglobulins / genetics*
  • Immunoglobulins / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Neurons / metabolism*
  • Phosphorylation
  • Protein Binding / genetics
  • Rats
  • SAP90-PSD95 Associated Proteins / genetics
  • SAP90-PSD95 Associated Proteins / metabolism
  • Synapses / genetics
  • Synapses / metabolism*
  • src Homology Domains / genetics

Substances

  • Cadm1 protein, rat
  • Cell Adhesion Molecules
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Immunoglobulins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mpp2 protein, rat
  • SAP90-PSD95 Associated Proteins