Background: SAP102 is a scaffolding protein that regulates NMDA receptor function. Results: Specific SAP102 spliced isoform is enriched at synapses to regulate NMDA receptor surface expression. Conclusion: I2 region-containing SAP102 is required for the regulation of subunit-specific NMDA receptor surface expression. Significance: This is the first study showing that SAP102 synaptic targeting is critical for regulating NMDA receptor trafficking.
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