Neuron
Volume 55, Issue 6, 20 September 2007, Pages 905-918
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Article
TARP Subtypes Differentially and Dose-Dependently Control Synaptic AMPA Receptor Gating

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Summary

A family of transmembrane AMPA receptor regulatory proteins (TARPs) profoundly affects the trafficking and gating of AMPA receptors (AMPARs). Although TARP 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 TARP subtype on the kinetics of AMPAR gating in heterologous cells and in neurons. We report a striking heterogeneity in the effects of TARP subtypes on AMPAR deactivation and desensitization, which we demonstrate controls the time course of synaptic transmission. In addition, we find that some TARP subtypes dramatically slow AMPAR activation kinetics. Synaptic AMPAR kinetics also depend on TARP expression level, suggesting a variable TARP/AMPAR stoichiometry. Analysis of quantal synaptic transmission in a TARP γ-4 knockout (KO) mouse corroborates our expression data and demonstrates that TARP subtype-specific gating of AMPARs contributes to the kinetics of native AMPARs at central synapses.

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4

Present address: SRI international, LA150 Menlo Park, CA 94025, USA.

5

Present address: Program in Neurobiology & Behavior, Columbia University, New York, NY 10032, USA.

6

Present address: Lilly Research Laboratories, Corporate Center, Indianapolis, IN 46285, USA.

7

These authors contributed equally to this work.