Abstract
This study was undertaken to provide a biophysical basis for the hypothesis that activity-dependent modulation of cadherin-mediated adhesion by transient changes of extracellular calcium ([Ca2+]e) is causally involved in coordination of synaptic plasticity. Characterization of homophilic N-cadherin binding by atomic force microscopy and laser tweezer trapping of N-cadherin-coated microbeads attached to the cell surface of cultured neuronal cells showed that adhesive activity of N-cadherin is effectively regulated between 0.3 and 0.8 mm [Ca2+]e. Furthermore, we show that an increase of [Ca2+]i, which is known to be essential for induction of synaptic plasticity, causes significant reduction of cadherin-mediated bead adhesion that could be completely suppressed by inhibition of actin depolymerization. The results of this study show that N-cadherin has ideal biophysical properties to serve as a Ca2+-dependent sensor for synaptic activity and, at the same time, is strategically located to control synaptic adhesion. A drop of [Ca2+]e and a concomitant increase of [Ca2+]i may act in concert to modulate N-cadherin-based adhesive contacts at synaptic sites.