Abstract
Cell adhesion molecules are important players at different stages of synapse formation, maintenance, and modulation of function. Among them, the neural cell adhesion molecule (N-CAM) promotes synapse formation, regulates synaptic strength, and contributes to memory formation and consolidation. Recent findings indicate that these effects are achieved by several mechanisms activated via N-CAM that is accumulated in postsynaptic densities in an activity-dependent manner. These include stabilization of synapses via homo- and heterophilic interactions of N-CAMs in the synaptic cleft, recruitment to and stabilization in synapses of the proteins and intracellular organelles associated with N-CAMs, and modulation of their postsynaptic activity via N-CAM-mediated modulation of kinases and phosphatases. Genetic variations in the N-CAM gene correlate with bipolar affective disorder in humans. Secreted extracellular cleavage products of N-CAMs accumulate in the hippocampus and prefrontal cortex of patients with schizophrenia and bipolar disorder and may thus interfere with homophilic or heterophilic interactions of N-CAMs. Since such dysfunctions are likely to relate to synaptic abnormalities, these findings lend further support to the notion that the N-CAM is an important player in the assembly and function of a unique invention: the synapse.