N-cadherin-dependent neuron-neuron interaction is required for the maintenance of activity-induced dendrite growth.

Formation of neural circuits depends on stable contacts between neuronal processes, mediated by interaction of cell adhesion molecules, including N-cadherin. In the present study, we found that activity-dependent dendrite arborization specifically requires N-cadherin-mediated extracellular neuron-neuron interaction, because the enhancement did not occur for neurons cultured in isolation or plated on an astrocyte monolayer and was abolished by a recombinant soluble N-cadherin ectodomain. Furthermore, depolarization elevated the level of membrane-associated cadherin/catenin complexes and surface N-cadherin. Importantly, surface N-cadherin elevation is specifically required for the maintenance of nascent dendrite arbors. Through loss- and gain-of-function approaches, we showed that N-cadherin-mediated dendrite growth requires association of the cadherin/catenin complex with the actin cytoskeleton. In summary, these results identify a previously unexplored and specific function for activity-induced, N-cadherin-mediated neuron-neuron contacts in the maintenance of dendrite arbors.