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

Neuroscience. 2002;115(4):1009-21. doi: 10.1016/s0306-4522(02)00532-8.

Abstract

Delta-catenin (or neural plakophilin-related arm-repeat protein/neurojungin) is primarily a brain specific member of the p120(ctn) subfamily of armadillo/beta-catenin proteins that play important roles in neuronal development. Our previous studies have shown that the ectopic expression of delta-catenin induces the formation of dendrite-like extensions and that the overexpression of delta-catenin promotes dendritic branching and increases spine density. Here we demonstrate that delta-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. Delta-catenin forms stable complexes with excitatory neurotransmitter receptors including ionotropic N-methyl-D-aspartic acid receptor 2A (NR2A), metabotropic glutamate receptor 1alpha (mGluR1alpha), as well as PSD-95 in vivo. In cultured primary embryonic neurons, delta-catenin clusters co-distribute with filamentous actin and resist detergent extraction. In dissociated hippocampal neurons overexpressing delta-catenin, glutamate stimulation leads to a rapid redistribution of delta-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, delta-catenin becomes down-regulated and its association with NR2A and mGluR1alpha in cultured neurons is diminished. These findings support a possible functional connection between delta-catenin and the glutamatergic excitatory synaptic signaling pathway during neuronal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Animals
  • Armadillo Domain Proteins
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Catenins
  • Cell Adhesion Molecules
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Cytoskeletal Proteins / drug effects
  • Cytoskeletal Proteins / metabolism*
  • Delta Catenin
  • Dendrites / drug effects
  • Dendrites / metabolism*
  • Dendrites / ultrastructure
  • Disks Large Homolog 4 Protein
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Fetus
  • Fluorescent Antibody Technique
  • Glutamic Acid / metabolism*
  • Glutamic Acid / pharmacology
  • Guanylate Kinases
  • Hippocampus / cytology
  • Hippocampus / embryology*
  • Hippocampus / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins / metabolism
  • Phosphoproteins
  • Pregnancy
  • Rats
  • Receptors, Glutamate / metabolism*
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Thiazoles / pharmacology
  • Thiazolidines

Substances

  • Armadillo Domain Proteins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Catenins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Dlg4 protein, rat
  • Excitatory Amino Acid Antagonists
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NR2A NMDA receptor
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Receptors, Glutamate
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Thiazoles
  • Thiazolidines
  • metabotropic glutamate receptor type 1
  • postsynaptic density proteins
  • Glutamic Acid
  • Guanylate Kinases
  • latrunculin A
  • Delta Catenin
  • Ctnnd1 protein, rat