Ser-1462 in the ESDV PDZ binding motif of NR2A is required for PSD-95 potentiation. The ESDV motif of NR2A was either deleted (NR2A-ΔESDV) or Ser-1462 was mutated to Ala (NR2A-S1462A) or Glu (NR2A-S1462E). These constructs were coexpressed with NR1–4b, which has the C2′ cassette containing a putative C-terminal PDZ binding motif (tSXV). (A–D) NMDA-elicited currents recorded from oocytes expressing NR1–4b with (A) NR2A wild type, (B) NR2A-ΔESDV, (C) NR2A-S1462A, or (D) NR2A-S1462E in the absence or presence of PSD-95. Mean values of current and PKC potentiation ratios are shown in the bar graphs to the right. (A) As in Figs. 1–5, coexpression of PSD-95 increased the basal responses but did not affect the final current after PKC potentiation, thus, reducing the PKC potentiation ratio. (B–D) All three mutants prevented the increase in response caused by PSD-95 expression and had no effect on PKC potentiation. See SI Table 2 for detailed values. Methods are as in Fig. 1.