A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex

The formation of functional synapses requires coordinated assembly of presynaptic transmitter release machinery and postsynaptic trafficking of functional receptors and scaffolds. Here, we demonstrate a critical role of presynaptic cadherin/catenin cell adhesion complexes in stabilizing functional synapses and spines in the developing neocortex. Importantly, presynaptic expression of stabilized β-catenin in either layer (L) 4 excitatory neurons or L2/3 pyramidal neurons significantly upregulated excitatory synaptic transmission and dendritic spine density in L2/3 pyramidal neurons, while its sparse postsynaptic expression in L2/3 neurons had no such effects. In addition, presynaptic β-catenin expression enhanced release probability of glutamatergic synapses. Newly identified β-catenin-interacting protein p140Cap is required in the presynaptic locus for mediating these effects. Together, our results demonstrate that cadherin/catenin complexes stabilize functional synapses and spines through anterograde signaling in the neocortex and provide important molecular evidence for a driving role of presynaptic components in spinogenesis in the neocortex. •Presynaptic β-catenin stabilizes spines and synapses in the developing neocortex•Symmetric cadherin/catenin complexes function asymmetrically during spinogenesis•p140Cap is a novel β-catenin-interacting partner•Presynaptic cadherin/catenin/p140Cap complexes regulate release probability Li et al. demonstrate an asymmetric role for the symmetric cadherin/catenin cell adhesion complex in synapse stabilization in the neocortex. This presynaptic function of β-catenin requires its novel binding partner p140Cap.