Clustering of surface NMDA receptors is mainly mediated by the C-terminus of GluN2A in cultured rat

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N-methyl-D-aspartate receptors(NMDARs) containing different GluN2 subunits play distinct roles in synaptic plasticity.Such differences may not only be determined by the channel properties, but also by differential surface distribution and synaptic localization.In the present study, using a Cy3-conjugated Fab fragment of the GFP antibody to label surface-located GluN2 subunits tagged with GFP at the N-terminus, we observed the membrane distribution patterns of GluN2A- or GluN2B-containing NMDARs in cultured rat hippocampal neurons.We found that surface NMDARs containing GluN2 A, but not those containing GluN2 B, were inclined to cluster at DIV7.Swapping the carboxyl termini of the GluN2 subunits completely reversed these distribution patterns.In addition, surface NMDARs containing GluN2 A were preferentially associated with PSD-95.Taken together, the results of our study suggest that the clustering distribution of GluN2 Acontaining NMDARs is determined by the GluN2 A C-terminus, and its interaction with PSD-95 plays an important role in this process. N-methyl-D-aspartate receptors (NMDARs) containing different GluN2 subunits play distinct roles in synaptic plasticity. Shuch differences may not only be determined by the channel properties, but also by differential surface distribution and synaptic localization. In the present study, using a Cy3-conjugated Fab fragment of the GFP antibody to label surface-localized GluN2 subunits tagged with GFP at the N-terminus, we observed the membrane distribution patterns of GluN2A- or GluN2B-containing NMDARs in cultured rat hippocampal neurons. We found that surface NMDARs containing GluN2 A, but not those containing GluN2 B, were inclined to cluster at DIV7. Wapping the carboxyl termini of the GluN2 subunits 2 had reversed the distribution pattern. In addition, surface NMDARs containing GluN2A were preferentially associated with PSD- together, the results of our study suggest that the clustering distribution of GluN2 Acontaining NMDARs is determined by the GluN2 A C-terminus, and its interaction with PSD-95 plays an important role in this process.
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