Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP

Neuron. 2003 Feb 20;37(4):625-38. doi: 10.1016/s0896-6273(02)01191-1.

Abstract

We identified four PDZ domain-containing proteins, syntenin, PICK1, GRIP, and PSD95, as interactors with the kainate receptor (KAR) subunits GluR5(2b,) GluR5(2c), and GluR6. Of these, we show that both GRIP and PICK1 interactions are required to maintain KAR-mediated synaptic function at mossy fiber-CA3 synapses. In addition, PKC alpha can phosphorylate ct-GluR5(2b) at residues S880 and S886, and PKC activity is required to maintain KAR-mediated synaptic responses. We propose that PICK1 targets PKC alpha to phosphorylate KARs, causing their stabilization at the synapse by an interaction with GRIP. Importantly, this mechanism is not involved in the constitutive recycling of AMPA receptors since blockade of PDZ interactions can simultaneously increase AMPAR- and decrease KAR-mediated synaptic transmission at the same population of synapses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Binding Sites / physiology
  • Brain Chemistry
  • Carrier Proteins / metabolism*
  • Cytoskeletal Proteins
  • Disks Large Homolog 4 Protein
  • Excitatory Postsynaptic Potentials / physiology
  • Guanylate Kinases
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins*
  • Isoenzymes / metabolism
  • Membrane Proteins*
  • Molecular Sequence Data
  • Mossy Fibers, Hippocampal / metabolism*
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Patch-Clamp Techniques
  • Phosphorylation
  • Protein Binding / physiology
  • Protein Kinase C / metabolism
  • Protein Kinase C-alpha
  • Protein Subunits / metabolism
  • Rats
  • Receptors, AMPA / metabolism*
  • Receptors, Kainic Acid / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Synapses / metabolism*
  • Syntenins
  • Two-Hybrid System Techniques

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cytoskeletal Proteins
  • DLG4 protein, human
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • GRIP1 protein, human
  • Grip1 protein, mouse
  • Grip1 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Isoenzymes
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • PICK1 protein, rat
  • Protein Subunits
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Recombinant Proteins
  • SDCBP protein, human
  • Syntenins
  • postsynaptic density proteins
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Guanylate Kinases