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.
Journal article
J Biol Chem
03/05/2002
277
15221 - 15224
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Binding Sites, COS Cells, Carrier Proteins, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Nuclear Proteins, Protein Subunits, Receptors, Glutamate, Recombinant Proteins, Sequence Alignment, Syntenins, Transfection