A transmembrane accessory subunit that modulates kainate-type glutamate receptors

Neuron. 2009 Feb 12;61(3):385-96. doi: 10.1016/j.neuron.2008.12.014.


Glutamate receptors play major roles in excitatory transmission in the vertebrate brain. Among ionotropic glutamate receptors (AMPA, kainate, NMDA), AMPA receptors mediate fast synaptic transmission and require TARP auxiliary subunits. NMDA receptors and kainate receptors play roles in synaptic transmission, but it remains uncertain whether these ionotropic glutamate receptors also have essential subunits. Using a proteomic screen, we have identified NETO2, a brain-specific protein of unknown function, as an interactor with kainate-type glutamate receptors. NETO2 modulates the channel properties of recombinant and native kainate receptors without affecting trafficking of the receptors and also modulates kainate-receptor-mediated mEPSCs. Furthermore, we found that kainate receptors regulate the surface expression of NETO2 and that NETO2 protein levels and surface expression are decreased in mice lacking the kainate receptor GluR6. The results show that NETO2 is a kainate receptor subunit with significant effects on glutamate signaling mechanisms in brain.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / ultrastructure
  • Cell Line
  • Cells, Cultured
  • Excitatory Postsynaptic Potentials / genetics
  • Female
  • GluK2 Kainate Receptor
  • Glutamic Acid / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Mutant Strains
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Patch-Clamp Techniques
  • Protein Subunits / genetics
  • Protein Subunits / isolation & purification
  • Protein Subunits / metabolism
  • Proteomics
  • Rats
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / isolation & purification
  • Receptors, Kainic Acid / metabolism*
  • Synaptic Membranes / metabolism*
  • Synaptic Membranes / ultrastructure
  • Synaptic Transmission / genetics*


  • Membrane Proteins
  • NETO2 protein, mouse
  • Protein Subunits
  • Receptors, Kainic Acid
  • Glutamic Acid