Glutamate-induced δ-catenin redistribution and dissociation from postsynaptic receptor complexes

δ-Catenin (or neural plakophilin-related arm-repeat protein/neurojungin) is primarily a brain specific member of the p120^ctn subfamily of armadillo/β-catenin proteins that play important roles in neuronal development. Our previous studies have shown that the ectopic expression of δ-catenin induces the formation of dendrite-like extensions and that the overexpression of δ-catenin promotes dendritic branching and increases spine density. Here we demonstrate that δ-catenin displays a dendritic distribution pattern in the adult mouse brain and is co-enriched with postsynaptic density-95 (PSD-95) in the detergent insoluble postsynaptic scaffolds. δ-Catenin forms stable complexes with excitatory neurotransmitter receptors including ionotropic N-methyl-D-aspartic acid receptor 2A (NR2A), metabotropic glutamate receptor 1α (mGluR1α), as well as PSD-95 in vivo. In cultured primary embryonic neurons, δ-catenin clusters co-distribute with filamentous actin and resist detergent extraction. In dissociated hippocampal neurons overexpressing δ-catenin, glutamate stimulation leads to a rapid redistribution of δ-catenin that can be attenuated by 6-cyano-7-nitroquinoxaline-2,3-dione and dizocilpine, selective inhibitors of ionotropic glutamate receptors. Upon glutamate receptor activation, δ-catenin becomes down-regulated and its association with NR2A and mGluR1α in cultured neurons is diminished. These findings support a possible functional connection between δ-catenin and the glutamatergic excitatory synaptic signaling pathway during neuronal development.