Cornichon proteins determine the subunit composition of synaptic AMPA receptors

Neuron. 2013 Mar 20;77(6):1083-96. doi: 10.1016/j.neuron.2013.01.017.


Cornichon-2 and cornichon-3 (CNIH-2/-3) are AMPA receptor (AMPAR) binding proteins that promote receptor trafficking and markedly slow AMPAR deactivation in heterologous cells, but their role in neurons is unclear. Using CNIH-2 and CNIH-3 conditional knockout mice, we find a profound reduction of AMPAR synaptic transmission in the hippocampus. This deficit is due to the selective loss of surface GluA1-containing AMPARs (GluA1A2 heteromers), leaving a small residual pool of synaptic GluA2A3 heteromers. The kinetics of AMPARs in neurons lacking CNIH-2/-3 are faster than those in WT neurons due to the fast kinetics of GluA2A3 heteromers. The remarkably selective effect of CNIHs on the GluA1 subunit is probably mediated by TARP γ-8, which prevents a functional association of CNIHs with non-GluA1 subunits. These results point to a sophisticated interplay between CNIHs and γ-8 that dictates subunit-specific AMPAR trafficking and the strength and kinetics of synaptic AMPAR-mediated transmission.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Excitatory Postsynaptic Potentials / physiology*
  • Hippocampus / physiology
  • Mice
  • Mice, Knockout
  • Organ Culture Techniques
  • Protein Subunits / chemistry
  • Protein Subunits / physiology
  • Receptors, AMPA / chemistry*
  • Receptors, AMPA / physiology*
  • Synapses / chemistry
  • Synapses / physiology
  • Synaptic Transmission / physiology*


  • Cnih2 protein, rat
  • Cnih3 protein, rat
  • Protein Subunits
  • Receptors, AMPA