Depolarization drives beta-Catenin into neuronal spines promoting changes in synaptic structure and function.
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.
Caltech/HHMI, Division of Biology, 216-76, 1200 East California Boulevard, Pasadena 91125, USA.
Sachiko
S
Murase
Eric
E
Mosser
Erin M
EM
Schuman
D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D007202:Indicators and Reagents / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics*; D011189:Potassium Chloride / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011993:Recombinant Fusion Proteins; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016704:Synapsins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D015534:Trans-Activators; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin
D015820:Cadherins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D004791:Enzyme Inhibitors; C092350:FM 4-64; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D011993:Recombinant Fusion Proteins; D016704:Synapsins; D015534:Trans-Activators; D051176:beta Catenin; C033652:postsynaptic density proteins; D049452:Green Fluorescent Proteins; D014443:Tyrosine; D011189:Potassium Chloride; D011505:Protein-Tyrosine Kinases