A neuronal role for SNAP-23 in postsynaptic glutamate receptor trafficking

Regulated exocytosis is essential for many biological processes, and many components of the protein trafficking machinery are ubiquitous. However, there are also exceptions such as SNAP-25, a neuron-specific SNARE protein, which is essential for synaptic vesicle release from presynaptic nerve terminals. In contrast, SNAP-23 is the ubiquitously-expressed SNAP-25 homologue that is critical for regulated exocytosis in non-neuronal cells. However, the role of SNAP-23 in neurons has not been elucidated. We now find that SNAP-23 is enriched in dendritic spines and colocalizes with constituents of the postsynaptic density, whereas SNAP-25 is restricted to axons. In addition, loss of SNAP-23 using genetically-altered mice or shRNA targeted to SNAP-23 leads to a dramatic decrease in NMDA receptor surface expression and NMDA receptor currents, whereas loss of SNAP-25 does not. Therefore SNAP-23 plays a unique role in the functional regulation of postsynaptic glutamate receptors.