AMPA Receptor Subunit-Specific Regulation by a Distinct Family of Type II TARPs

SummaryAMPA-type glutamate receptors (GluRs) play major roles in excitatory synaptic transmission. Neuronal AMPA receptors comprise GluR subunits and transmembrane AMPA receptor regulatory proteins (TARPs). Previous studies identified five mammalian TARPs, γ-2 (or stargazin), γ-3, γ-4, γ-7, and γ-8, that enhance AMPA receptor function. Here, we classify γ-5 as a distinct class of TARP that modulates specific GluR2-containing AMPA receptors and displays properties entirely dissimilar from canonical TARPs. γ-5 increases peak currents and decreases the steady-state currents selectively from GluR2-containing AMPA receptors. Furthermore, γ-5 increases rates of GluR2 deactivation and desensitization and decreases glutamate potency. Remarkably, all effects of γ-5 require editing of GluR2 mRNA. Unlike other TARPs, γ-5 modulates GluR2 without promoting receptor trafficking. We also find that γ-7 regulation of GluR2 is dictated by mRNA editing. These data establish γ-5 and γ-7 as a separate family of “type II TARPs” that impart distinct physiological features to specific AMPA receptors.