Cadherins and catenins at synapses: roles in synaptogenesis and synaptic plasticity

Abstract

Synapse formation involves reciprocal interactions between cells resulting in formation of a structure optimized for efficient information transfer. Recent work has implicated constituents of the cadherin-catenin cell-adhesion complex in both synapse formation and plasticity. In this review, we describe recent interesting discoveries on mechanisms of cadherin complex function, in addition to regulating adhesion, that are relevant for understanding the role of this complex in synaptogenesis and plasticity. We describe how this complex acts via (i) recruitment/stabilization of intracellular partners; (ii) regulation of intracellular signaling pathways; (iii) regulation of cadherin surface levels, stability and turnover; (iv) stabilization of receptors; and (v) regulation of gene expression. These exciting discoveries provide insights into novel functional roles of the complex beyond regulating cell adhesion.

Figure 1

Schematic representation of hippocampal excitatory synapse formation and localization of the cadherin–catenin complex at different stages. (a) Synaptogenesis is initiated by the formation of nascent contacts between dendritic filopodia and axons. At these stages, N-cadherin in distributed evenly along the synaptic structure. This is followed by (b) contact stabilization and clustering of cadherin and (c) maturity. A mature synapse is characterized by a stable presynaptic terminal that contains vesicles primed for neurotransmitter release and a postsynaptic density that contains the receptors and scaffolding proteins. In the adult, cadherin is localized to distinct regions bordering the mature active zone, termed as the puncta adherentia. Both β-catenin and α-catenin are known to colocalize with cadherin at these junctions. Recent studies in nonneuronal cells indicate that the binding of α-catenin to β-catenin and actin are mutually exclusive, with the monomer form having a higher affinity for β-catenin and the dimer having a higher affinity for actin. Although p120ctn and δ-catenin are known to be at synapses, their localization at the electron microscope level and during development is unclear.

Figure 2

A partial list of proteins that interact with components of the cadherin–catenin complex. Components of the complex bind to a variety of scaffolding proteins, receptors, kinases and phosphatases.