Molecular modification of N-cadherin in response to synaptic activity

The relationship between adhesive interactions across the synaptic cleft an d synaptic function has remained elusive. At certain CNS synapses, pre- to postsynaptic adhesion is mediated at least in part by neural (N-) cadherin. Here, we demonstrate that upon depolarization of hippocampal neurons in cu lture by K+ treatment, or application of NMDA or alpha-latrotoxin, synaptic N-cadherin dimerizes and becomes markedly protease resistant. These proper ties are indices of strong, stable, enhanced cadherin-mediated intercellula r adhesion. N-cadherin retained protease resistance for at least 2 hr after recovery, while other surface molecules, including other cadherins, were c ompletely degraded. The acquisition of protease resistance and dimerization of N-cadherin is not dependent on new protein synthesis, nor is it accompa nied by internalization of N-cadherin. By immunocytochemistry, we found tha t high K+ selectively induces surface dispersion of N-cadherin, which, afte r recovery, returns to synaptic puncta. N-cadherin dispersion under K+ trea tment parallels the rapid expansion of the presynaptic membrane consequent to the massive vesicle fusion that occurs with this type of depolarization. In contrast, with NMDA application, N-cadherin does not disperse but does acquire enhanced protease resistance and dimerizes. Our data strongly sugge st that synaptic adhesion is dynamically and locally controlled, and modula ted by synaptic activity.