title: Cornichon proteins determine the subunit composition of synaptic AMPA receptors.
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.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Herring
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Suh
authors.forename: Chan-Ying
authors.initials: CY
authors.lastname: Zheng
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Blankenship
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Roche
authors.forename: Roger A
authors.initials: RA
authors.lastname: Nicoll
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D021122:Protein Subunits / Q000737:chemistry / Q000502:physiology; D018091:Receptors, AMPA / Q000737:chemistry* / Q000502:physiology*; D013569:Synapses / Q000737:chemistry / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA; C539313:Cnih2 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C539314:Cnih3 protein, rat