Functional assembly of AMPA and kainate receptors is mediated by several discrete protein-protein interactions

Neuron. 2001 Jul 19;31(1):103-13. doi: 10.1016/s0896-6273(01)00333-6.


Functional heterogeneity of ionotropic glutamate receptors arises not only from the existence of many subunits and isoforms, but also from combinatorial assembly creating channels with distinct properties. This heteromerization is subtype restricted and thought to be determined exclusively by the proximal extracellular N-terminal domain of the subunits. However, using functional assays for heteromer formation, we show that, besides the N-terminal domain, the membrane sector and the C-terminal part of S2 are critical determinants for the formation of functional channels. Our results are compatible with a model where the N-terminal domain only mediates the initial subunit associations into dimers, whereas for the assembly of the full functional tetramer, compatibility of the other regions is required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Membrane / physiology
  • Female
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Macromolecular Substances
  • Magnesium Chloride / pharmacology
  • Membrane Potentials / drug effects
  • Models, Chemical
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Polymerase Chain Reaction
  • Protein Subunits
  • Receptors, AMPA / chemistry*
  • Receptors, AMPA / genetics
  • Receptors, AMPA / physiology*
  • Receptors, Kainic Acid / chemistry*
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / physiology*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • Xenopus laevis
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Macromolecular Substances
  • Protein Subunits
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Recombinant Fusion Proteins
  • Magnesium Chloride
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid