Depolarization drives beta-Catenin into neuronal spines promoting changes in synaptic structure and function

Neuron. 2002 Jul 3;35(1):91-105. doi: 10.1016/s0896-6273(02)00764-x.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cadherins / metabolism
  • Cells, Cultured
  • Cytoskeletal Proteins / drug effects
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Dendrites / drug effects
  • Dendrites / metabolism*
  • Dendrites / ultrastructure
  • Disks Large Homolog 4 Protein
  • Enzyme Inhibitors / pharmacology
  • Fluorescent Dyes
  • 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
  • Quaternary Ammonium Compounds
  • 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

Substances

  • Cadherins
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Enzyme Inhibitors
  • FM 4-64
  • Fluorescent Dyes
  • Indicators and Reagents
  • Intracellular Signaling Peptides and Proteins
  • Luminescent Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Recombinant Fusion Proteins
  • Synapsins
  • Trans-Activators
  • beta Catenin
  • postsynaptic density proteins
  • Green Fluorescent Proteins
  • Tyrosine
  • Potassium Chloride
  • Protein-Tyrosine Kinases