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

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Binding Sites, Brain Chemistry, Carrier Proteins, Excitatory Postsynaptic Potentials, Hippocampus, Intracellular Signaling Peptides and Proteins, Isoenzymes, Membrane Proteins, Molecular Sequence Data, Mossy Fibers, Hippocampal, Mutagenesis, Site-Directed, Nerve Tissue Proteins, Nuclear Proteins, Patch-Clamp Techniques, Phosphorylation, Protein Binding, Protein Kinase C, Protein Kinase C-alpha, Protein Subunits, Rats, Receptors, AMPA, Receptors, Kainic Acid, Recombinant Proteins, Synapses, Syntenins, Two-Hybrid System Techniques
Date: Feb. 20, 2003
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