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

Abstract

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 formediating 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.