Proteomics of brain synapses and molecular dissection of synaptic subdomains

Synapses form the nuts and bolts of the brain. Synaptic transmission involves an intricate network of synaptic proteins that forms the molecular machinery underlying transmitter release, activation of transmitter receptors, and signal transduction cascades. It is generally believed that neuronal activity-dependent change of synaptic efficacy is at the basis of learning and memory and is encoded by sequential molecular events at the synapse. In the past 2-3 years, a number of proteomics studies have been performed on synaptic subdomains, including synaptic vesicles, postsynaptic density, synaptic lipid raft, synapse protein complexes, as well as on synaptic protein PTMs, notably phosphorylation. The activity-dependent dynamics of protein constituents of the synapse are starting to be examined by quantitative proteomics. It is anticipated that these analyses will yield novel insights into the organization of the synapse, and will generate testable hypotheses of synapse function and regulation both in health and disease.