TARP subtypes differentially and dose-dependently control synaptic AMPA receptor gating.

A family of transmembrane AMPA receptor regulatory proteins profoundly affects the trafficking and gating of AMPA receptors (AMPARs). Although subtypes are differentially expressed throughout the CNS, it is unclear whether this imparts functional diversity to AMPARs in distinct neuronal populations. Here, we examine the effects of each Tduanyu37 subtype on the kinetics of AMPAR gating in heterologous cells and in neurons. We report a striking heterogeneity in the effects of Tduanyu37 subtypes on AMPAR deactivation and desensitization, which we demonstrate controls the time course of synaptic transmission. In addition, we find that some Tduanyu37 subtypes dramatically slow AMPAR activation kinetics. Synaptic AMPAR kinetics also depend on Tduanyu37 expression level, suggesting a variable stoichiometry. Analysis of quantal synaptic transmission in a Tduanyu37 gamma-4 knockout (KO) mouse corroborates our expression data and demonstrates that Tduanyu37 subtype-specific gating of AMPARs contributes to the kinetics of native AMPARs at central synapses.

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