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.
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We thank Y.-X. Wang for help with immunogold labeling, J.D. Badger II for preparing primary neuron cultures and M. Park (Stanford University) for helpful technical comments. We also thank the National Institute of Neurological Disorders and Stroke Light Imaging Facility, particularly C. Smith. In addition, we would like to acknowledge the National Institute of Neurological Disorders and Stroke sequencing facility. This research was supported by the National Cancer Institute Intramural Research Program (P.A.R.), the National Institute of Neurological Disorders and Stroke Intramural Research Program (Y.H.S. and K.W.R.), the Integrative Neural Immune Program (Y.H.S. fellowship), and the intramural program of the National Institute on Deafness and other Communication Disorders (R.S.P. and R.J.W.).
The authors declare no competing financial interests.
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Suh, Y., Terashima, A., Petralia, R. et al. A neuronal role for SNAP-23 in postsynaptic glutamate receptor trafficking. Nat Neurosci 13, 338–343 (2010) doi:10.1038/nn.2488
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