TARP Subtypes Differentially and Dose-Dependently Control Synaptic AMPA Receptor Gating

Aaron D. Milstein, Wei Zhou, Siavash Karimzadegan, David S. Bredt, Roger A. Nicoll

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)905-918
Number of pages14
JournalNeuron
Volume55
Issue number6
DOIs
StatePublished - Sep 20 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • CELLBIO
  • SIGNALING
  • SYSNEURO

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