Structural and compositional diversity in the kainate receptor family

Cell Rep. 2021 Oct 26;37(4):109891. doi: 10.1016/j.celrep.2021.109891.


The kainate receptors (KARs) are members of the ionotropic glutamate receptor family and assemble into tetramers from a pool of five subunit types (GluK1-5). Each subunit confers distinct functional properties to a receptor, but the compositional and stoichiometric diversity of KAR tetramers is not well understood. To address this, we first solve the structure of the GluK1 homomer, which enables a systematic assessment of structural compatibility among KAR subunits. Next, we analyze single-cell RNA sequencing data, which reveal extreme diversity in the combinations of two or more KAR subunits co-expressed within the same cell. We then investigate the composition of individual receptor complexes using single-molecule fluorescence techniques and find that di-heteromers assembled from GluK1, GluK2, or GluK3 can form with all possible stoichiometries, while GluK1/K5, GluK2/K5, and GluK3/K5 can form 3:1 or 2:2 complexes. Finally, using three-color single-molecule imaging, we discover that KARs can form tri- and tetra-heteromers.

Keywords: cryo-electron microscopy; iGluRs; kainate receptors; single-cell RNA sequencing; single-molecule Förster resonance energy transfer; single-molecule pull-down.

Publication types

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

MeSH terms

  • Cell Membrane / chemistry
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • HEK293 Cells
  • Humans
  • Protein Multimerization*
  • Protein Subunits
  • Receptors, Kainic Acid / chemistry*
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / metabolism*


  • Protein Subunits
  • Receptors, Kainic Acid