Fig. 1: GluA2 CTD-interactions exert a modulatory but nonessential influence on receptor synaptic anchoring.

a Schematic of heteromeric AMPAR architecture (blue - GluA1, red - GluA2) demonstrating the four ___domain layers (NTD - N-terminal or amino-terminal ___domain; LBD ligand-binding ___domain, TMD transmembrane ___domain, CTD C-terminal ___domain) and association with the auxiliary subunit TARP γ8 (green), with the studied interaction domains highlighted yellow. b GluA2 CTD protein sequence with interaction mutations indicated. c Dual recording configuration involves simultaneous patch-clamp of untransfected (nonfluorescent, Untrans.) and single-cell electroporated (SCE) neurons, depicted on fluorescence image of EGFP expressing CA1 neurons after SCE. d–e Dual synaptic recordings on GluA2Q construct expression. Full-length GluA2Q robustly reduces synaptic rectification index d and increases AMPAR EPSC amplitudes e. No CTD modifications altered this phenotype, demonstrating a nonessential role for this ___domain in synaptic receptor anchoring d–e. Example dual recordings (untransfected cell—Untrans., grey; transfected cell—red) for GluA2Q with (right) and without (left) ΔNSF mutation are depicted with individual sweeps (light) and average response (bold). Stimulation is indicated as a triangle. GluA2Q ΔNTD causes a robust reduction in the rectification index of synaptic responses f and a reduction in AMPAR EPSC amplitudes g. These changes are partially alleviated by some GluA2Q CTD mutations such as NSF site mutagenesis (ΔNSF) or GluA1 intracellular ___domain (ICD) exchange f–g. Prenormalised data are presented in Supplementary Figure 1f–g, and data values and statistical details are presented in Supplementary Table 1. Bars represent mean values, * indicates p < 0.05, **p < 0.01 and ***p < 0.001. Source data are provided as a source data file.