title: Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins.
abstract: Transmembrane AMPA receptor regulatory proteins (TARPs) and cornichon proteins (CNIH-2/3) independently modulate AMPA receptor trafficking and gating. However, the potential for interactions of these subunits within an AMPA receptor complex is unknown. Here, we find that TARPs γ-4, γ-7, and γ-8, but not γ-2, γ-3, or γ-5, cause AMPA receptors to "resensitize" upon continued glutamate application. With γ-8, resensitization occurs with all GluA subunit combinations; however, γ-8-containing hippocampal neurons do not display resensitization. In recombinant systems, CNIH-2 abrogates γ-8-mediated resensitization and modifies AMPA receptor pharmacology and gating to match that of hippocampal neurons. In hippocampus, γ-8 and CNIH-2 associate in postsynaptic densities and CNIH-2 protein levels are markedly diminished in γ-8 knockout mice. Manipulating neuronal CNIH-2 levels modulates the electrophysiological properties of extrasynaptic and synaptic γ-8-containing AMPA receptors. Thus, γ-8 and CNIH-2 functionally interact with common hippocampal AMPA receptor complexes to modulate synergistically kinetics and pharmacology.
authors.affiliation: Department of Neuroscience, Eli Lilly and Company, Indianapolis, IN 46285, USA. katoak@lilly.com
authors.forename: Akihiko S
authors.initials: AS
authors.lastname: Kato
authors.forename: Martin B
authors.initials: MB
authors.lastname: Gill
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Ho
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tu
authors.forename: Edward R
authors.initials: ER
authors.lastname: Siuda
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Yue-Wei
authors.initials: YW
authors.lastname: Qian
authors.forename: Eric S
authors.initials: ES
authors.lastname: Nisenbaum
authors.forename: Susumu
authors.initials: S
authors.lastname: Tomita
authors.forename: David S
authors.initials: DS
authors.lastname: Bredt
mesh_terms: D000818:Animals; D015220:Calcium Channels; D002478:Cells, Cultured; D057809:HEK293 Cells; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology*; D055366:Synaptic Potentials / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D018091:Receptors, AMPA; C539313:Cnih2 protein, rat; D009419:Nerve Tissue Proteins; C539314:Cnih3 protein, rat; C532482:TARP gamma-4 protein, mouse; C519955:TARP gamma-7 protein, mouse; C515550:TARP gamma-8 protein, mouse