Abstract
Activity-induced changes in adhesion molecules may coordinate presynaptic and postsynaptic plasticity. Here, we demonstrate that beta-catenin, which mediates interactions between cadherins and the actin cytoskeleton, moves from dendritic shafts into spines upon depolarization, increasing its association with cadherins. beta-catenin's redistribution was mimicked or prevented by a tyrosine kinase or phosphatase inhibitor, respectively. Point mutations of beta-catenin's tyrosine 654 altered the shaft/spine distribution: Y654F-beta-catenin-GFP (phosphorylation-prevented) was concentrated in spines, whereas Y654E-beta-catenin-GFP (phosphorylation-mimic) accumulated in dendritic shafts. In Y654F-expressing neurons, the PSD-95 or associated synapsin-I clusters were larger than those observed in either wild-type-beta-catenin or also Y654E-expressing neurons. Y654F-expressing neurons exhibited a higher minifrequency. Thus, neural activity induces beta-catenin's redistribution into spines, where it interacts with cadherin to influence synaptic size and strength.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Cadherins / metabolism
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Cells, Cultured
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Cytoskeletal Proteins / drug effects
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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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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Enzyme Inhibitors / pharmacology
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Fluorescent Dyes
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Green Fluorescent Proteins
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Hippocampus / cytology
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Hippocampus / growth & development*
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Hippocampus / metabolism*
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Indicators and Reagents / metabolism
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins / metabolism
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Male
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Proteins
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Mutation / genetics
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Nerve Tissue Proteins / metabolism
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / genetics*
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Potassium Chloride / pharmacology
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Protein Transport / drug effects
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Protein Transport / genetics*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Pyridinium Compounds
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Quaternary Ammonium Compounds
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Rats
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Recombinant Fusion Proteins
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Synapses / drug effects
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Synapses / metabolism*
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Synapses / ultrastructure
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Synapsins / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / genetics*
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Trans-Activators*
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Tyrosine / genetics
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Tyrosine / metabolism
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beta Catenin
Substances
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Cadherins
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Ctnnb1 protein, rat
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Cytoskeletal Proteins
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Enzyme Inhibitors
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FM 4-64
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Fluorescent Dyes
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Indicators and Reagents
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Pyridinium Compounds
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Quaternary Ammonium Compounds
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Recombinant Fusion Proteins
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Synapsins
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Trans-Activators
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beta Catenin
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postsynaptic density proteins
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Green Fluorescent Proteins
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Tyrosine
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Potassium Chloride
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Protein-Tyrosine Kinases