Neural cell adhesion molecules and synapse regulation

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.