Fig. 2

Wnts exert both pre- and post-synaptic effects. Presynaptic Wnt signaling through Wnt3 and Wnt7 acts through a Dvl pathway to stabilize microtubules and also influences presynaptic clustering of acetylcholine receptors (AChRs) through an APC-mediated mechanism (upper left). Presynaptic β-catenin is also involved in synapse formation and maintenance through cell–cell adhesion mechanisms, though a relationship between this and Wnt signaling remains speculative. Wnt5a-activated signaling through the Ror kinase is also thought to contribute to an increase in presynaptic sites through a mechanism that has not yet been determined (upper right). Postsynaptic Wnt signaling driven by Wnt5a probably acts through a Dvl/Rac/JNK pathway to regulate the actin cytoskeleton (lower right). Application of Wnt3a, Wnt 7a, or Wnt7b is sufficient to induce β-catenin translocation to the nucleus and may well also influence synapses (not shown). As in the presynaptic terminal, β-catenin is present in the postsynaptic density of excitatory synapses where it is involved in cell–cell adhesion. Also not shown is a highly divergent postsynaptic pathway established at the Drosophila neuromuscular junction involving cleavage and translocation of Fzd receptors to the nucleus; there is evidence that a mechanistically similar pathway operates at some vertebrate synapses