Editors' ChoiceSynaptic Plasticity

Cross Synaptic Communication

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Science's STKE  09 Jul 2002:
Vol. 2002, Issue 140, pp. tw240-TW240
DOI: 10.1126/stke.2002.140.tw240

Two groups report how changes in the cadherin-catenin-cytoskeleton interactions alter presynaptic and postsynaptic structure and synaptic activity. Cadherins are calcium-dependent homophilic adhesion proteins that bind to β-catenin, which in turn binds to α-catenin, which interacts with the cytoskeleton. The interaction between cadherin and β-catenin is regulated by phosphorylation with a decreased interaction between the two when β-catenin is phosphorylated. Togashi et al. disrupted cadherin interactions in cultured hippocampal neurons labeled for presynaptic and postsynaptic marker proteins. In cultures transfected with a dominant negative form of N-cadherin (DN-cad) that could not form homophilic interactions, but could still bind β-catenin, the postsynaptic dendritic spine morphology was altered to an elongated structure lacking the typical mushroom-shaped ending. Presynaptic activity was decreased (measured by uptake of the dye FM-64 as an indicator of vesicle cycling), and postsynaptic marker proteins were more diffusely located than in control cultures. The same types of changes were observed in cultured hippocampal neurons from αN-catenin (a neuronal-specific isoform) knockout mice, which die shortly after birth. Murase et al. observed that depolarization or treatment of hippocampal slices with a tyrosine kinase inhibitor increased the intensity of punctate β-catenin staining. In cultured hippocampal neurons, depolarization increased β-catenin in the spine and decreased β-catenin in the dendritic shaft. Treatments that pharmacologically manipulate kinase and phosphatase activities also altered β-catenin distrubution. The changes in β-catenin distribution were mimicked by tyrosine mutants of β-catenin: Y654E mimicked the phosphorylated state of β-catenin, with decreased cadherin binding and decreased accumulation in the spine; and Y654F mimicked the nonphosphorylated state of β-catenin, with increased cadherin binding and increased accumulation in dendritic spines. Changes in synaptic activity also correlated with β-catenin distribution. Synapses with the Y654 mutation had increased miniature excitatory postsynaptic currents and increased FM-64 dye uptake, indicating enhanced synaptic activity. Thus, changes in the dendritic morphology and postsynaptic cadherin-catenin complex can transmit information across the synapse to regulate presynaptic activity and morphology (see Goda for more discussion).

H. Togashi, K. Abe, A. Mizoguchi, K. Takaoka, O. Chisaka, M. Takeichi, Cadherin regulates dendritic spine morphogenesis. Neuron 35, 77-89 (2002). [Online Journal]

S. Murase, E. Mosser, E. M. Schuman, Depolarization drives β-catenin into neuronal spines promoting changes in synaptic structure and function. Neuron 35, 91-105 (2002). [Online Journal]

Y. Goda, Cadherins communicate structural plasticity of presynaptic and postsynaptic terminals. Neuron 35, 1-7 (2002). [Online Journal]

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