Neuron
Volume 37, Issue 4, 20 February 2003, Pages 625-638
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Article
Rapid and Differential Regulation of AMPA and Kainate Receptors at Hippocampal Mossy Fibre Synapses by PICK1 and GRIP

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Abstract

We identified four PDZ domain-containing proteins, syntenin, PICK1, GRIP, and PSD95, as interactors with the kainate receptor (KAR) subunits GluR52b, GluR52c, 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, PKCα can phosphorylate ct-GluR52b at residues S880 and S886, and PKC activity is required to maintain KAR-mediated synaptic responses. We propose that PICK1 targets PKCα 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.

Cited by (0)

1

These authors contributed equally to the work.

2

Present address: INSERM U583, Institut de Biologie, 4 Boulevard Henri IV, 34060 Montpellier, Cedex, France.

3

Present address: Department of Biosciences, Division of Animal Physiology, Biocenter 3 (Viikinkaari 1), P.O. Box 65, University of Helsinki, Finland.

4

Present address: AGY Therapeutics, Inc., 290 Utah Avenue, South San Francisco, California 94080.

5

Present address: Université de Bordeaux II, UMR.5091/Physiologie Cellulaire de la Synapse, Institut.

6

Present address: Novartis Pharma AG, Nervous System Research, CH-4002 Basel, Switzerland.

7

Present address: Laboratory for Neuronal Circuit Dynamics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-Shi, Saitama 351-0198, Japan.

8

Present address: Max-Planck Institut fur Experimentelle, Medizin, Abt. Molekulare Neurobiologie, Hermann-Rein Strasse 3, D-37075, Gottingen, Germany.