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

• DOI: 10.1038/nn.2488
• Publication Date: 2010-01-31T18:43:57Z
• Authors: Young Ho Suh; Akira Terashima; Ronald S Petralia; Robert J Wenthold; John T R Isaac; Katherine W Roche; Paul A Roche
• Keywords: Neurons; 0301 basic medicine; Dendritic Spines; Cell Membrane; Mice, Transgenic; Dendrites; In Vitro Techniques; Qb-SNARE Proteins; Hippocampus; Receptors, N-Methyl-D-Aspartate; Article; Axons; Cell Line; Membrane Potentials; Rats; Rats, Sprague-Dawley; Mice; 03 medical and health sciences; Receptors, Glutamate; Synapses; Animals; Humans; Qc-SNARE Proteins

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 that is essential for synaptic vesicle release from presynaptic nerve terminals. In contrast, SNAP-23 is a ubiquitously expressed SNAP-25 homolog that is critical for regulated exocytosis in non-neuronal cells. However, the role of SNAP-23 in neurons has not been elucidated. We found that SNAP-23 was enriched in dendritic spines and colocalized with constituents of the postsynaptic density, whereas SNAP-25 was restricted to axons. In addition, loss of SNAP-23 using genetically altered mice or shRNA targeted to SNAP-23 led to a marked decrease in NMDA receptor surface expression and NMDA receptor currents, whereas loss of SNAP-25 did not. SNAP-23 is therefore important for the functional regulation of postsynaptic glutamate receptors.