Synapses are adhesive junctions. This is a widely acknowledged and accepted fact, but most early studies on the mechanisms of CNS synapse development focused on the events and components that contribute directly to neurotransmission. For several years, the synaptic cleft was ignored. The discovery that members of the cadherin family of cell-adhesion molecules were concentrated at synapses1,2 renewed interest in an old debate that had focused on the morphological similarities between adherens junctions, which are generated by

'Fishberg Department of Neuroscience, Mount Sinai School of Medicine, 1425 Madison Avenue Box 1065, New York, NY 10029, USA; [email protected] and [email protected]

cadherin adhesion and synaptic junctions3,4. Cadherins were not the first adhesion proteins to be found at synapses, but they were the first that were known to be capable of generating cell-cell junctions. They also cluster at synapses early in synaptogenesis and different cadherins delineate functionally distinct synapse types. These findings collectively suggested that cadherins could be critical components for synapse assembly and could potentially guide synapse specificity5. Experimental findings now support that cadherin-based adhesion is important for synapse assembly, synapse stabilization, dendritic spine morphology, and functional plasticity.

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