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Science 323 (5919): 1313-1319

Copyright © 2009 by the American Association for the Advancement of Science

Functional Proteomics Identify Cornichon Proteins as Auxiliary Subunits of AMPA Receptors

Jochen Schwenk,1* Nadine Harmel,1* Gerd Zolles,1* Wolfgang Bildl,1 Akos Kulik,4 Bernd Heimrich,4 Osamu Chisaka,6 Peter Jonas,3 Uwe Schulte,1,2 Bernd Fakler,1,5{dagger} Nikolaj Klöcker1{dagger}

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.

1 Institute of Physiology II, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany.
2 Logopharm GmbH, Engesserstrasse 4, 79108 Freiburg, Germany.
3 Institute of Physiology I, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany.
4 Institute of Anatomy and Cell Biology, University of Freiburg, Albertstrasse 23, 79104 Freiburg, Germany.
5 Center for Biological Signaling Studies (bioss), Albertstrasse 10, 79104 Freiburg, Germany.
6 Department of Cell and Developmental Biology, Kyoto University, Kyoto 606-8502, Japan.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: bernd.fakler{at}physiologie.uni-freiburg.de (B.F.) or nikolaj.kloecker{at}physiologie.uni-freiburg.de (N.K.)

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