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J Biol Chem. 2002 May 3;277(18):15221-4. Epub 2002 Mar 12.

The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs.

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  • 1Department of Anatomy, Medical Research Council Centre of Synaptic Plasticity, Medical School, University of Bristol, Bristol BS8 1TD, United Kingdom.

Abstract

Using sequence homology searches, yeast two-hybrid assays and glutathione S-transferase (GST)-pull-down approaches we have identified a series of glutamate receptor subunits that interact differentially with the PDZ proteins GRIP, PICK1, and syntenin. GST-pull-down experiments identified more interactions than detected by yeast two-hybrid assays. We report several receptor-protein interactions, strong ones include: (i) GRIP and syntenin with mGluR7a, mGluR4a, and mGluR6; (ii) PICK1 and GRIP with mGluR3; and (iii) syntenin with all forms of GluR1-4 and mGluR7b. We further characterized the novel mGluR7a-GRIP interaction found both in yeast two-hybrid and GST-pull-down assays and observed that mGluR7a localization overlapped with GRIP with in hippocampal neurons. The wide range of targets for PICK1, GRIP, and syntenin suggests they may represent a molecular mechanism that can concentrate and/or regulate a number of different receptors at a common site on a synapse. These data also suggest that the structural determinants involved in PDZ interactions are more complex than originally envisaged.

PMID:
11891216
[PubMed - indexed for MEDLINE]
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