The Cadherin Family of Cell Adhesion Molecules: Multiple Roles in Synaptic Plasticity

Abstract

Cadherins are cell adhesion molecules that are critically important for establishing brain structure and connectivity during early development. They are enriched at synapses and, by virtue of a number of properties including homophilic recognition and molecular diversity, have been implicated in the generation of synaptic specificity. Cadherins also participate in remodeling synaptic architecture and modifying the strength of the synaptic signal, thereby retaining an active role in synaptic structure, function, and plasticity, which extends beyond initial development. Cadherins have been implicated in the induction of long-term potentiation (LTP) of hippocampal synaptic strength, a cellular model for learning and memory. LTP is associated with the synthesis and recruitment of N-cadherin to newly forming synaptic junctions, induces molecular changes to N-cadherin indicative of augmented adhesive force, and can be prevented when cadherin adhesion is blocked. NMDA receptor activation, which is critically required for synaptic plasticity, may provide a signal that regulates the molecular configuration of synaptic N-cadherin, and therefore the strength of adhesion across the synaptic cleft. Additionally, there exists at the synapse a pool of surface cadherins that is untethered to the actin cytoskeleton and capable of a rapid and reversible dispersion along the plasmalemma under conditions of strong activity. These observations suggest that synaptic activity dynamically regulates both the strength and the localization of cadherin-cadherin bonds across the synaptic junctional interface, changes that may be crucial for regulating synaptic plasticity.