N-cadherin-mediated cell adhesion is regulated by extracellular Zn2+

Synapses in the central nervous system (CNS) are highly dynamic structures that undergo reorganisation in response to synaptic activity. Dysfunctional structural synaptic plasticity is associated with impaired brain function and several neurological disorders. As response to synaptic activity, dendritic spines of excitatory synapses were reported to undergo alterations in their molecular structure and morphology leading to increased postsynaptic density size and spine volume. For these structural changes a transient activity-dependent weakening of synaptic adhesion will be necessary. Here, we report that zinc can modulate N-cadherin-mediated adhesion. Quantification of binding activity was performed using laser tweezer technique. Our results show that increased levels of zinc abolished N-cadherin binding without altering the number of N-cadherin molecules expressed at the cell surface. Furthermore, zinc directly interacted with N-cadherin and the regulatory role was found to take place under physiological zinc concentrations within minutes. Given that zinc is released at zincergic synapses in the CNS, our findings may contribute to mechanistic insights in the interplay between zinc signalling, activation of glutamate receptors and downstream pathways, and the coordination of pre- and postsynaptic changes via transsynaptic cell adhesion complexes, all finally contributing to synaptic plasticity.