The first proteins have now been identified that initiate the formation of synapses. One is SynCAM 1, a synaptic cell adhesion molecule that connects pre- and postsynaptic sides. SynCAM 1 is the founding member of a family of immunoglobulin proteins with three extracellular Ig domains, a single transmembrane region, and a short cytosolic tail that includes interaction motifs with cytoskeletal; regulators and scaffolding proteins. SynCAMs are highly enriched in brain and are prominent components of purified synaptic plasma membranes.
They can engage in homophilic interactions, bridging across two neurons, but can also interact with other SynCAM molecules in select heterophilic combinations. Importantly, SynCAM proteins alters neurotransmission and act across the nascent synaptic cleft to induce new, fully functional presynaptic terminals. This activity allowed us to reconstitute excitatory synaptic transmission for the first time (see Figure). Our recent studies of SynCAM 1 in mouse models have demonstrated that this protein not only drives synapse formation in vivo but also maintains the increase in synapses that it induces. In addition, SynCAM 1 regulates synaptic plasticity and up- and down-regulates the ability to learn.