Synapse adhesion: a dynamic equilibrium conferring stability and flexibility

Abstract

Cell adhesion molecules (CAMs) linked to cytoskeleton generate stable cell-cell junctions. Cadherins provide a canonical example, but paradoxically, they participate in a multitude of transient and regulatable interactions. Their extracellular binding generates weak adhesion that is modified by clustering; interactions with F-actin are regulated, can be transient, and can alter F-actin dynamics. Additionally, cadherin recycling from the cell surface can modify the size and location of junctions and strength of adhesion. In epithelial cells, this ongoing dynamic behavior is important for maintaining stable junctions. Recent work supports that cadherins act similarly at synapses where their actions are likely to be shared by integrins and other actin-linked CAMs. Together the collaborative activities of such CAMs provide a stable, but flexible structure that can promote and support changes in synapse shape and size while maintaining stable junctions to permit information flow.

Figure 1

Cartoon illustrates some of the dynamic aspects of cadherin localization and interactions with actin cytoskeleton at developing (left) and mature (right) synapses. Arrows indicate transient interactions: extracellular domain swapping in cis and in trans and intracellular clustering. Actin is represented as stable condensations as well as elongated, more dynamic filaments. Alpha-actinin also has a dynamic relationship with actin and cadherin that is not well understood, but α-catenin promotes cadherin mobility [44]. The precise binding relationship between cadherins and actin is not known, but may involve cis interactions with nectins, vezatin or synaptotagmin-like proteins, or β-catenin binding to actin binding proteins [–57].