Recruitment of the kainate receptor subunit glutamate receptor 6 by cadherin/catenin complexes.
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, beta-catenin, and p120 catenin, as well as with the associated proteins calcium calmodulin-dependent serine kinase and Velis, but not with alpha-catenin. In glutathione S-transferase-pulldown experiments, beta-catenin interacts, although indirectly, with the last 14 aa of GluR6. Transfected myc-GluR6 colocalizes with beta-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.
Coussen
Françoise
F
Centre National de la Recherche Scientifique Unité Mixte de Recherche 5091, Institut François Magendie, Paris 75005, France.
Normand
Elisabeth
E
Marchal
Cécile
C
Costet
Pierre
P
Choquet
Daniel
D
Lambert
Mireille
M
Mège
René-Marc
RM
Mulle
Christophe
C
D000818:Animals; D001923:Brain Chemistry; D015820:Cadherins / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins / Q000378:metabolism; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003433:Crosses, Genetic; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D051528:Guanylate Kinases; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin; D000095002:Delta Catenin; D000097806:GluK2 Kainate Receptor
D015820:Cadherins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051528:Guanylate Kinases; D046911:Macromolecular Substances; D009703:Nucleoside-Phosphate Kinase; D010750:Phosphoproteins; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051176:beta Catenin; D000095002:Delta Catenin; D000097806:GluK2 Kainate Receptor; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C495268:Ctnnb1 protein, rat; C106868:CASK kinases