Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex

Neuron. 2000 Jul;27(1):107-19. doi: 10.1016/s0896-6273(00)00013-1.

Abstract

Compartmentalization of glutamate receptors with the signaling enzymes that regulate their activity supports synaptic transmission. Two classes of binding proteins organize these complexes: the MAGUK proteins that cluster glutamate receptors and AKAPs that anchor kinases and phosphatases. In this report, we demonstrate that glutamate receptors and PKA are recruited into a macromolecular signaling complex through direct interaction between the MAGUK proteins, PSD-95 and SAP97, and AKAP79/150. The SH3 and GK regions of the MAGUKs mediate binding to the AKAP. Cell-based studies indicate that phosphorylation of AMPA receptors is enhanced by a SAP97-AKAP79 complex that directs PKA to GluR1 via a PDZ domain interaction. As AMPA receptor phosphorylation is implicated in regulating synaptic plasticity, these data suggest that a MAGUK-AKAP complex may be centrally involved.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Binding, Competitive / physiology
  • Blotting, Western
  • Carrier Proteins / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Disks Large Homolog 4 Protein
  • Guanylate Kinases
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microscopy, Confocal
  • Nerve Tissue Proteins / physiology
  • Neurons / metabolism
  • Nucleoside-Phosphate Kinase / metabolism*
  • Precipitin Tests
  • Protein Binding / physiology
  • Rats
  • Receptors, AMPA / metabolism
  • Receptors, AMPA / physiology
  • Receptors, Glutamate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Signal Transduction / physiology*
  • Synaptic Transmission / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Disks Large Homolog 4 Protein
  • Dlg1 protein, rat
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mpp2 protein, rat
  • Nerve Tissue Proteins
  • Receptors, AMPA
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • postsynaptic density proteins
  • Cyclic AMP-Dependent Protein Kinases
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases
  • glutamate receptor ionotropic, AMPA 1