Glutamate-induced delta-catenin redistribution and dissociation from postsynaptic receptor complexes.
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.
Jones
S B
SB
Department of Anatomy and Cell Biology, The Brody School of Medicine at East Carolina University, 7N 84 Brody Sciences Building, 600 Moye Boulevard, Greenville, NC 27858, USA.
Lanford
G W
GW
Chen
Y-H
YH
Morabito
M
M
Moribito
M
M
Kim
K
K
Lu
Q
Q
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D051186:Armadillo Domain Proteins; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D051177:Catenins; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005333:Fetus; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins; D011247:Pregnancy; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D000095002:Delta Catenin
D051186:Armadillo Domain Proteins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C501449:Dlg4 protein, rat; D018691:Excitatory Amino Acid Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C120997:NR2A NMDA receptor; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D013844:Thiazoles; D053778:Thiazolidines; C104077:metabotropic glutamate receptor type 1; C033652:postsynaptic density proteins; D018698:Glutamic Acid; D051528:Guanylate Kinases; C037067:latrunculin A; D000095002:Delta Catenin; C000722355:Ctnnd1 protein, rat