Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors Journal Article


Author(s): Schwenk, Jochen; Harmel, Nadine; Zolles, Gerd; Bildl, Wolfgang; Kulik, Ákos; Heimrich, Bernd; Chisaka, Osamu; Jonas, Peter; Schulte, Uwe; Fakler, Bernd; Klocker, Nikolaj
Article Title: Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors
Affiliation
Abstract: Glutamate receptors of the AMPA-subtype (AMPARs), together with the transmembrane AMPAR regulatory proteins (TARPs), mediate fast excitatory synaptic transmission in the mammalian brain. Here, we show by proteomic analysis that the majority of AMPARs in the rat brain are coassembled with two members of the cornichon family of transmembrane proteins, rather than with the TARPs. Coassembly with cornichon homologs 2 and 3 affects AMPARs in two ways: Cornichons increase surface expression of AMPARs, and they alter channel gating by markedly slowing deactivation and desensitization kinetics. These results demonstrate that cornichons are intrinsic auxiliary subunits of native AMPARs and provide previously unknown molecular determinants for glutamatergic neurotransmission in the central nervous system.
Keywords: Animals; Rats; Mice; Kinetics; Immunohistochemistry; Signal Transduction; Synaptic Transmission; Patch-Clamp Techniques; Ion Channel Gating; Cell Membrane/metabolism; Glutamic Acid/metabolism; Membrane Proteins/chemistry/metabolism; Protein Subunits/chemistry/metabolism; Proteomics; Synapses/metabolism; Xenopus; Brain/cytology/metabolism; Neurons/metabolism; Receptors, AMPA/chemistry/metabolism
Journal Title: Science
Volume: 323
Issue 5919
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Publication Place: United States
Date Published: 2009-01-01
Start Page: 1313
End Page: 9
DOI: 10.1126/science.1167852
Open access: no