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PMID:12123611
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| Citation |
Murase, S, Mosser, E and Schuman, EM (2002) Depolarization drives beta-Catenin into neuronal spines promoting changes in synaptic structure and function. Neuron 35:91-105 |
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| 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. |
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| Keywords |
Animals; Animals, Newborn; Cadherins/metabolism; Cells, Cultured; Cytoskeletal Proteins/drug effects; Cytoskeletal Proteins/genetics; Cytoskeletal Proteins/metabolism; Dendrites/drug effects; Dendrites/metabolism; Dendrites/ultrastructure; Enzyme Inhibitors/pharmacology; Fluorescent Dyes/diagnostic use; Green Fluorescent Proteins; Hippocampus/cytology; Hippocampus/growth & development; Hippocampus/metabolism; Indicators and Reagents/metabolism; Intracellular Signaling Peptides and Proteins; Luminescent Proteins/metabolism; Male; Membrane Potentials/drug effects; Membrane Potentials/physiology; Membrane Proteins; Mutation/genetics; Nerve Tissue Proteins/metabolism; Neuronal Plasticity/drug effects; Neuronal Plasticity/genetics; Potassium Chloride/pharmacology; Protein Transport/drug effects; Protein Transport/genetics; Protein-Tyrosine Kinases/antagonists & inhibitors; Protein-Tyrosine Kinases/metabolism; Pyridinium Compounds/diagnostic use; Quaternary Ammonium Compounds/diagnostic use; Rats; Recombinant Fusion Proteins; Synapses/drug effects; Synapses/metabolism; Synapses/ultrastructure; Synapsins/metabolism; Synaptic Transmission/drug effects; Synaptic Transmission/genetics; Trans-Activators; Tyrosine/genetics; Tyrosine/metabolism; beta Catenin |
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