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 (NCAM) promotes synapse formation, regulates synaptic strength, and contributes to memory formation and consolidation. These effects are achieved by several mechanisms activated via NCAM that is accumulated in postsynaptic densities in an activity-dependent manner and include stabilization of synapses via homo- and heterophilic interactions of the cognate isoforms of NCAM in the synaptic cleft, recruitment to and stabilization in synapses of the proteins and intracellular organelles associated with distinct isoforms of NCAM, and modulation of their pre- and postsynaptic activity via NCAM-mediated modulation of kinases and phosphatases. Genetic variations in the NCAM gene correlate with bipolar affective disorders in humans. Soluble extracellular cleavage products of NCAM accumulate in the hippocampus and prefrontal cortex of patients with schizophrenia and bipolar disorders and may thus interfere with homophilic or heterophilic interactions of NCAM. Since such dysfunctions are likely to relate to synaptic abnormalities, these findings lend further support to the notion that NCAM is an important player in the assembly and function of a unique invention: the synapse.