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C200112200v1
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Papers In Press, published online ahead of print March 12, 2002
J. Biol. Chem, 10.1074/jbc.C200112200
Submitted on February 25, 2002
Revised on March 11, 2002
Accepted on March 11, 2002

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

Hélène Hirbec, Olga Perestenko, Atsushi Nishimune, Guido Meyer, Shigetada Nakanishi, Jeremy M. Henley, and Kumlesh K. Dev

Unit of Neurodegeneration, Novartis Pharma AG, Basel CH-4002

Corresponding Author: kumlesh_k.dev{at}pharma.novartis.com

Using sequence homology searches, yeast two-hybrid assays and GST-pulldown approaches we have identified a series of glutamate receptor subunits that interact differentially with the PDZ proteins GRIP, PICK1 and syntenin. GST-pulldown 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 characterised the novel mGluR7a-GRIP interaction found both in yeast two-hybrid and GST-pulldown assays and observed that mGluR7a localisation 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.


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