Structural and functional insights into transmembrane AMPA receptor regulatory protein complexes

J Gen Physiol. 2019 Dec 2;151(12):1347-1356. doi: 10.1085/jgp.201812264. Epub 2019 Oct 15.

Abstract

Fast excitatory neurotransmission is mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptor (AMPAR). AMPARs initiate depolarization of the postsynaptic neuron by allowing cations to enter through their ion channel pores in response to binding of the neurotransmitter glutamate. AMPAR function is dramatically affected by auxiliary subunits, which are regulatory proteins that form various complexes with AMPARs throughout the brain. The most well-studied auxiliary subunits are the transmembrane AMPAR regulatory proteins (TARPs), which alter the assembly, trafficking, localization, kinetics, and pharmacology of AMPARs. Recent structural and functional studies of TARPs and the TARP-fold germ cell-specific gene 1-like (GSG1L) subunit have provided important glimpses into how auxiliary subunits regulate the function of synaptic complexes. In this review, we put these recent structures in the context of new functional findings in order to gain insight into the determinants of AMPAR regulation by TARPs. We thus reveal why TARPs display a broad range of effects despite their conserved modular architecture.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Claudins / metabolism
  • Glutamic Acid / metabolism
  • Humans
  • Membrane Proteins / metabolism*
  • Neurons / metabolism
  • Protein Transport / physiology
  • Receptors, AMPA / metabolism*
  • Synaptic Transmission / physiology

Substances

  • Claudins
  • Membrane Proteins
  • Receptors, AMPA
  • Glutamic Acid

Associated data

  • PDB/5WEO
  • PDB/6QKC
  • PDB/5VHY