Sigma-1 Receptors Modulate NMDA Receptor Function

Abstract

The sigma-1 receptor (σ-1R) is an endoplasmic reticulum (ER) protein that modulates a number of ion channels. It is hypothesized that σ-1Rs activated with agonist translocate to the plasma membrane. The σ-1R potentiates N-methyl-D-aspartate Receptors (NMDARs), important constituents of synaptic plasticity. NMDARs are anchored in the plasma membrane by Postsynaptic Density Protein-95 (PSD-95). The mechanism behind σ-1R modulation of NMDARs is not known. The results of my investigation confirm that σ-1Rs localize extrasomatically. Following σ-1R activation, σ-1R localization to dendrites and postsynaptic densities (PSDs) is upregulated. Unpublished work from our lab has shown that σ-1Rs associate with PSD-95 and NMDARs. Furthermore, immunocytochemistry (ICC) showed σ-1R colocalization with PSD-95 and NMDAR subunits. After σ-1R activation there was significantly increased colocalization between σ-1R, PSD-95, and GluN2B. Overall, this study may have provided insight into the molecular mechanism behind σ-1R modulation of NMDARs, which could have implications in the understanding of synaptic plasticity.