AMPA Receptors

Abstract

Neuronal communication relies on rapid signalling via chemical synapses. Glutamate receptors mediate the majority of excitatory neurotransmission in the central nervous system. At excitatory synapses, glutamate is released and binds to a variety of glutamate receptors. Among these, α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptors mediate most of the fast excitatory synaptic transmission. In addition, AMPA receptors play a critical role in the synaptic plasticity underlying learning and memory and neuronal development. When the regulation of synaptic expression of AMPA receptors goes awry, devastating neurological and neuropsychiatric diseases can occur. Since their cloning in the 1990s, much has been learned about the structure, assembly and trafficking of AMPA receptors. Exciting new advances in AMPA receptor research have offered unprecedented opportunities to understand dynamic regulation of AMPA receptor structure and function in brain.

Key Concepts:

  • AMPA receptors mediate fast glutamatergic synaptic transmission.

  • Crystal structure of AMPA receptors shows unexpected domain organisation.

  • Regulation of synaptic expression of AMPA receptors is highly dynamic.

  • AMPA receptor modulation and/or trafficking mediates LTP.

  • AMPA receptors are structurally diverse.

  • Subunit composition of AMPA receptors varies at different synapses.

  • Post‐translational modifications of AMPA receptors regulate trafficking and function.

  • AMPA receptor dysfunction is involved in diseases.

Keywords: glutamate; AMPA receptor; excitatory synapse; crystal structure; receptor phosphorylation; palmitoylation; ubiquitination; synaptic plasticity; receptor trafficking; stargazin; cornichon; AMPAKines

Figure 1.

Topologies of the AMPA receptor and its auxiliary subunits. Schematics of an AMPA receptor subunit in the plasma membrane (left), transmembrane AMPA receptor regulatory protein (TARP, middle) and cornichon (CNIH, right). NTD, extracellular ligand‐binding domains (S1 and S2), transmembrane domains, the flip/flop alternative splicing site and the RNA‐editing sites (Q/R and R/G) are also shown for the AMPA receptor. Figure adapted from Jackson and Nicoll . © Elsevier.

Figure 2.

Schematic of an AMPA receptor. AMPA receptors are tetrameric cation channels composed of various combinations of different subunits. Note that membrane region 2 (M2) is a reentrant loop, not a transmembrane domain, that underlies the channel pore formation.

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Lu, Wei, and Roche, Katherine W(Dec 2013) AMPA Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000231.pub3]