Structural and Functional Architecture of AMPA-Type Glutamate Receptors and Their Auxiliary Proteins

Neuron. 2017 May 17;94(4):713-730. doi: 10.1016/j.neuron.2017.04.009.


AMPA receptors (AMPARs) are tetrameric ion channels that together with other ionotropic glutamate receptors (iGluRs), the NMDA and kainate receptors, mediate a majority of excitatory neurotransmission in the central nervous system. Whereas NMDA receptors gate channels with slow kinetics, responsible primarily for generating long-term synaptic potentiation and depression, AMPARs are the main fast transduction elements at synapses and are critical for the expression of plasticity. The kinetic and conductance properties of AMPARs are laid down during their biogenesis and are regulated by post-transcriptional RNA editing, splice variation, post-translational modification, and subunit composition. Furthermore, AMPAR assembly, trafficking, and functional heterogeneity depends on a large repertoire of auxiliary subunits-a feature that is particularly striking for this type of iGluR. Here, we discuss how the subunit structure, stoichiometry, and auxiliary subunits generate a heterogeneous plethora of receptors, each tailored to fulfill a vital role in fast synaptic signaling and plasticity.

Keywords: AMPA receptor; AMPAR assembly; AMPAR gating; Cryo-EM; LTP; TARP; auxiliary subunit; excitatory synaptic transmission; glutamate receptor; plasticity.

Publication types

  • Review

MeSH terms

  • Animals
  • Glutamic Acid / metabolism*
  • Humans
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology
  • Protein Isoforms
  • Protein Processing, Post-Translational
  • Protein Subunits
  • Protein Transport
  • RNA Processing, Post-Transcriptional
  • Receptors, AMPA / genetics*
  • Receptors, AMPA / metabolism
  • Receptors, AMPA / physiology
  • Synaptic Transmission / genetics*
  • Synaptic Transmission / physiology


  • Protein Isoforms
  • Protein Subunits
  • Receptors, AMPA
  • Glutamic Acid