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The Journal of Neuroscience, August 1, 2002, 22(15):6426-6436

Recruitment of the Kainate Receptor Subunit Glutamate Receptor 6 by Cadherin/Catenin Complexes

Françoise Coussen¹, Elisabeth Normand¹, Cécile Marchal¹, Pierre Costet², Daniel Choquet¹, Mireille Lambert³, René-Marc Mège³, and Christophe Mulle¹

¹ Centre National de la Recherche Scientifique Unité Mixte de Recherche 5091, Institut François Magendie and ² Laboratoire de Transgénèse Université Bordeaux 2, Bordeaux 33077, France, and ³ Institut National de la Santé et de la Recherche Médicale U440, Institut du Fer à Moulin, Paris 75005, France

Kainate receptors modulate synaptic transmission by acting either at presynaptic or at postsynaptic sites. The precise localization of kainate receptors as well as the mechanisms of targeting and stabilization of these receptors in neurons are largely unknown. We have generated transgenic mice expressing the kainate receptor subunit glutamate receptor 6 (GluR6) bearing an extracellular myc epitope (myc-GluR6), in forebrain neurons, in which it assembles with endogenous kainate receptor subunits. In transgenic mice crossed with GluR6-deficient mice, myc-GluR6 efficiently rescues the missing subunit. Immunoprecipitation of transgenic brain extracts with anti-myc antibodies demonstrates an interaction with cadherins, -catenin, and p120 catenin, as well as with the associated proteins calcium calmodulin-dependent serine kinase and Velis, but not with -catenin. In glutathione S-transferase-pulldown experiments, -catenin interacts, although indirectly, with the last 14 aa of GluR6. Transfected myc-GluR6 colocalizes with -catenin at cell-cell junctions in non-neuronal cells. Finally, activation of N-cadherins by ligand-covered latex beads recruits GluR6 to cadherin/catenin complexes. These results suggest an important role for cadherin/catenin complexes in the stabilization of kainate receptors at the synaptic membrane during synapse formation and remodeling.

Key words: kainate receptors; cadherin/catenin complexes; transgenic mice; synaptic organization; protein-protein interactions; CASK/Veli complexes

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22156426-11$05.00/0

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