Referenced in: none

Automatically associated channels: Slo1

Title: Cornichon proteins determine the subunit composition of synaptic AMPA receptors.

Authors: Bruce E Herring, Yun Shi, Young Ho Suh, Chan-ying Zheng, Sabine M Blankenship, Katherine W Roche, Roger A Nicoll

Journal, date & volume: Neuron, 2013 Mar 20 , 77, 1083-96

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23522044

Abstract
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.