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
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / metabolism
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Animals
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Armadillo Domain Proteins
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Catenins
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Cell Adhesion Molecules
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cells, Cultured
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Cytoskeletal Proteins / drug effects
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Cytoskeletal Proteins / metabolism*
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Delta Catenin
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Dendrites / drug effects
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Dendrites / metabolism*
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Dendrites / ultrastructure
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Disks Large Homolog 4 Protein
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Excitatory Amino Acid Antagonists / pharmacology
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Female
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Fetus
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Fluorescent Antibody Technique
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Glutamic Acid / metabolism*
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Glutamic Acid / pharmacology
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Guanylate Kinases
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Hippocampus / cytology
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Hippocampus / embryology*
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Hippocampus / metabolism
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins / metabolism
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Phosphoproteins
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Pregnancy
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Rats
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Receptors, Glutamate / metabolism*
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Receptors, Metabotropic Glutamate / drug effects
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Receptors, Metabotropic Glutamate / metabolism
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Synaptic Membranes / drug effects
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Synaptic Membranes / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Thiazoles / pharmacology
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Thiazolidines
Substances
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Armadillo Domain Proteins
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Bridged Bicyclo Compounds, Heterocyclic
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Catenins
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Cell Adhesion Molecules
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Cytoskeletal Proteins
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Disks Large Homolog 4 Protein
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Dlg4 protein, mouse
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Dlg4 protein, rat
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Excitatory Amino Acid Antagonists
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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NR2A NMDA receptor
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Nerve Tissue Proteins
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Phosphoproteins
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Receptors, Glutamate
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Receptors, Metabotropic Glutamate
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Receptors, N-Methyl-D-Aspartate
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Thiazoles
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Thiazolidines
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metabotropic glutamate receptor type 1
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postsynaptic density proteins
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Glutamic Acid
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Guanylate Kinases
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latrunculin A
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Delta Catenin
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Ctnnd1 protein, rat