TY - JOUR
T1 - Depolarization drives β-catenin into neuronal spines promoting changes in synaptic structure and function
AU - Murase, Sachiko
AU - Mosser, Eric
AU - Schuman, Erin M.
N1 - Funding Information:
We thank Bryan Smith for help with data analysis and members of the Schuman lab for helpful discussion and criticism. We thank Tim Ryan for helpful discussions, Mark Stopfer for help with the analysis and critique of the manuscript, Michael Tsung and Holli Weld for making beautiful cultured hippocampal neurons, and Gilles Laurent for critique of the manuscript. This work was funded by the Computational Molecular Biology program at Caltech. E.M.S. is an HHMI Assistant Investigator.
PY - 2002/7/3
Y1 - 2002/7/3
N2 - Activity-induced changes in adhesion molecules may coordinate presynaptic and postsynaptic plasticity. Here, we demonstrate that β-catenin, which mediates interactions between cadherins and the actin cytoskeleton, moves from dendritic shafts into spines upon depolarization, increasing its association with cadherins. β-catenin's redistribution was mimicked or prevented by a tyrosine kinase or phosphatase inhibitor, respectively. Point mutations of β-catenin's tyrosine 654 altered the shaft/spine distribution: Y654F-β-catenin-GFP (phosphorylation-prevented) was concentrated in spines, whereas Y654E-β-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-β-catenin or also Y654E-expressing neurons. Y654F-expressing neurons exhibited a higher minifrequency. Thus, neural activity induces β-catenin's redistribution into spines, where it interacts with cadherin to influence synaptic size and strength.
AB - Activity-induced changes in adhesion molecules may coordinate presynaptic and postsynaptic plasticity. Here, we demonstrate that β-catenin, which mediates interactions between cadherins and the actin cytoskeleton, moves from dendritic shafts into spines upon depolarization, increasing its association with cadherins. β-catenin's redistribution was mimicked or prevented by a tyrosine kinase or phosphatase inhibitor, respectively. Point mutations of β-catenin's tyrosine 654 altered the shaft/spine distribution: Y654F-β-catenin-GFP (phosphorylation-prevented) was concentrated in spines, whereas Y654E-β-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-β-catenin or also Y654E-expressing neurons. Y654F-expressing neurons exhibited a higher minifrequency. Thus, neural activity induces β-catenin's redistribution into spines, where it interacts with cadherin to influence synaptic size and strength.
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U2 - 10.1016/S0896-6273(02)00764-X
DO - 10.1016/S0896-6273(02)00764-X
M3 - Article
C2 - 12123611
AN - SCOPUS:0037014456
VL - 35
SP - 91
EP - 105
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -