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Ubiquitously expressed throughout the CNS, Nectins are Ig-like cell adhesion molecules that exert multiple effects on cell migration, proliferation, survival, and differentiation. Members of the Nectin family (Nectin-1 to -4) are structurally characterized by three extracellular Ig-like domains, a single transmembrane region, and an intracellular C-terminal PDZ domain. Nectins preferentially form heterophilic complexes to promote calcium-independent cell-cell adhesion through trans interaction of their extracellular domains. To facilitate synaptic adhesion, Nectin molecules are anchored to the Actin cytoskeleton via a PDZ-dependent interaction with Afadin, which in turn binds F-Actin. During the generation of new synapses, Nectins are believed to form a relatively weak adhesion complex which is strengthened following the recruitment of Cadherin molecules.