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

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Abstract

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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Figure 1: SNAP-25 and SNAP-23 are differentially expressed in neurons.
Figure 2: Endogenous SNAP-23 is enriched at excitatory synapses on dendritic spines.
Figure 3: NMDA receptor surface expression is reduced in SNAP-23 heterozygous mice.
Figure 4: SNAP-23, but not SNAP-25, regulates surface expression of NMDA receptors.
Figure 5: SNAP-23 regulates the recycling of the NMDA receptor subunit NR2B.
Figure 6: Knockdown of SNAP-23 causes a reduction in NMDA-evoked currents and NMDA EPSCs in CA1 pyramidal neurons.

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Acknowledgements

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.).

Author information

P.A.R. and K.W.R. designed and supervised the experiments and wrote the manuscript. Immunogold electron microscopy was performed by R.S.P. and R.J.W. The electrophysiology study was carried out by A.T. and J.T.R.I. All other experiments were performed by Y.H.S.

Correspondence to Katherine W Roche or Paul A Roche.

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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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