High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes.
AMPA-type glutamate receptors (AMPARs) are responsible for a variety of processes in the mammalian brain including fast excitatory neurotransmission, postsynaptic plasticity, or synapse development. Here, with comprehensive and quantitative proteomic analyses, we demonstrate that native AMPARs are macromolecular complexes with a large molecular diversity. This diversity results from coassembly of the known AMPAR subunits, pore-forming GluA and three types of auxiliary proteins, with 21 additional constituents, mostly secreted proteins or transmembrane proteins of different classes. Their integration at distinct abundance and stability establishes the heteromultimeric architecture of native AMPAR complexes: a defined core with a variable periphery resulting in an apparent molecular mass between 0.6 and 1 MDa. The additional constituents change the gating properties of AMPARs and provide links to the protein dynamics fundamental for the complex role of AMPARs in formation and operation of glutamatergic synapses.
Institute of Physiology, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany.
Jochen
J
Schwenk
Nadine
N
Harmel
Aline
A
Brechet
Gerd
G
Zolles
Henrike
H
Berkefeld
Catrin Swantje
CS
Müller
Wolfgang
W
Bildl
David
D
Baehrens
Björn
B
Hüber
Akos
A
Kulik
Nikolaj
N
Klöcker
Uwe
U
Schulte
Bernd
B
Fakler
D000818:Animals; D001921:Brain / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011487:Protein Conformation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D040901:Proteomics; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics; D014981:Xenopus
D021122:Protein Subunits; D018091:Receptors, AMPA