Mapping the proteome of the synaptic cleft through peroxidase-based reporter protein SynCAM1-HRP

Synapses are the brain’s functional units connecting neurons into circuits that underlie memory and behavior. These specialized neuronal junctions are heterogenic in function and molecular composition, reflecting diverse health and disease states. Progress over the past years has shown that trans-synaptic adhesion molecules mediate synapse formation, specification, and differentiation during development. Among the prominently expressed synaptic cleft proteins are SynCAMs, a group of immunoglobulin molecules that engage in homo- and heterophilic interactions and that instruct synapse formation and guide synaptic maturation and that are specific for excitatory synapses. The current study describes the use of peroxidase-mediated proximity labeling to map the proteome of excitatory synapses using SynCAM1 as a reporter protein.