Assembly and stoichiometry of the AMPA receptor and transmembrane AMPA receptor regulatory protein complex.
Glutamate is a major excitatory neurotransmitter in the vertebrate brain. AMPA-type glutamate receptors mediate fast excitatory transmission. AMPA receptors assemble with transmembrane AMPA receptor regulatory protein (TARP) auxiliary subunits and function as native ion channels. However, the assembly and stoichiometry of AMPA receptor and TARP complexes remain unclear. Here, we developed a novel strategy to determine the assembly and stoichiometry of this protein complex and found that functional AMPA receptors indeed assembled as a tetramer in a dimer-of-dimers structure. Furthermore, we found that the AMPA receptor auxiliary subunit, TARP, had a variable stoichiometry (1-4 TARP units) on AMPA receptors and that 1 TARP unit was sufficient to modulate AMPA receptor activity. In neurons, TARP had fixed and minimum stoichiometry on AMPA receptors. This fundamental composition of the AMPA receptor/TARP complex is important for the elucidation of the molecular machinery that underlies synaptic transmission.
Kim
Kwang S
KS
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Yan
Dan
D
Tomita
Susumu
S
D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006388:Hemagglutinins / Q000378:metabolism; D007814:Larva; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011487:Protein Conformation; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics; D013269:Stochastic Processes; D014158:Transcription, Genetic; D014981:Xenopus; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D015220:Calcium Channels; D049452:Green Fluorescent Proteins; D006388:Hemagglutinins; D009687:Nuclear Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C491911:Cacng2 protein, rat; C413185:TARP