AMPA receptor tetramerization is mediated by Q/R editing

Neuron. 2003 Nov 13;40(4):763-74. doi: 10.1016/s0896-6273(03)00668-8.


AMPA-type glutamate receptors (AMPARs) play a major role in excitatory synaptic transmission and plasticity. Channel properties are largely dictated by their composition of the four subunits, GluR1-4 (or A-D). Here we show that AMPAR assembly and subunit stoichiometry are determined by RNA editing in the pore loop. We demonstrate that editing at the GluR2 Q/R site regulates AMPAR assembly at the step of tetramerization. Specifically, edited R subunits are largely unassembled and ER retained, whereas unedited Q subunits readily tetramerize and traffic to synapses. This assembly mechanism restricts the number of the functionally critical R subunits in AMPAR tetramers. Therefore, a single amino acid residue affects channel composition and, in turn, controls ion conduction through the majority of AMPARs in the brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Arginine / metabolism
  • Brain / metabolism*
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • HeLa Cells
  • Humans
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Models, Molecular
  • Protein Subunits / genetics*
  • Protein Subunits / metabolism
  • Protein Transport / genetics
  • RNA Editing / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, AMPA / genetics*
  • Receptors, AMPA / metabolism
  • Synaptic Membranes / genetics*
  • Synaptic Membranes / metabolism
  • Synaptic Transmission / genetics


  • Ion Channels
  • Protein Subunits
  • RNA, Messenger
  • Receptors, AMPA
  • Arginine
  • glutamate receptor ionotropic, AMPA 2