Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors.
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.
Schwenk
Jochen
J
Institute of Physiology II, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany.
Harmel
Nadine
N
Zolles
Gerd
G
Bildl
Wolfgang
W
Kulik
Akos
A
Heimrich
Bernd
B
Chisaka
Osamu
O
Jonas
Peter
P
Schulte
Uwe
U
Fakler
Bernd
B
Klöcker
Nikolaj
N
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D015640:Ion Channel Gating; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission; D014981:Xenopus; D009419:Nerve Tissue Proteins
D018698:Glutamic Acid; D008565:Membrane Proteins; D021122:Protein Subunits; D018091:Receptors, AMPA; C539313:Cnih2 protein, rat; D009419:Nerve Tissue Proteins; C539314:Cnih3 protein, rat