Cadherins are transmembrane adhesion proteins whose cytoplasmic domains bind to b-catenin, which in turn binds to a-catenin, which interacts with the actin cytoskeleton. The interaction between cadherin and b-catenin is regulated by phosphorylation, with a decreased interaction between the two when b-catenin is phosphorylated. Togashi et al. disrupted cadherin-cadherin interactions in cultured hippocampal neurons with a dominant negative form of N-cadherin, lacking the extracellular domain but still able to bind b-catenin. Postsynaptic dendritic spines became thinner and longer as compared to the usual mushroom shape. Presynaptic activity decreased (as reflected in less vesicle cycling), and postsynaptic proteins were more diffuse than in control cultures. Murase et al. show that depolarization or treatment of hippocampal neurons with a tyrosine kinase inhibitor shifted b-catenin into dendritic spines and promoted its interaction with cadherin. These changes could be mimicked by mutation: Y654F (corresponding to the unphosphorylated state) accumulated in spines, and these synapses displayed increased spontaneous neurotransmitter release. Thus, changes in dendritic morphology and the postsynaptic cadherin-catenin complex occur in concert with presynaptic activity. — NG
Neuron35, 77; 91 (2002).