title: AMPA receptor tetramerization is mediated by Q/R editing.
abstract: AMPA-type glutamate receptors (AMPARs) play a major role in excitatory synaptic transmission and plasticity. Channel properties are largely dictated by their composition of the four subunits, GluR1-4 (or A-D). Here we show that AMPAR assembly and subunit stoichiometry are determined by RNA editing in the pore loop. We demonstrate that editing at the GluR2 Q/R site regulates AMPAR assembly at the step of tetramerization. Specifically, edited R subunits are largely unassembled and ER retained, whereas unedited Q subunits readily tetramerize and traffic to synapses. This assembly mechanism restricts the number of the functionally critical R subunits in AMPAR tetramers. Therefore, a single amino acid residue affects channel composition and, in turn, controls ion conduction through the majority of AMPARs in the brain.
authors: Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA. ig@mrc-lmb.cam.ac.uk
authors: Ingo H
authors: IH
authors: Greger
authors: Latika
authors: L
authors: Khatri
authors: Xiangpeng
authors: X
authors: Kong
authors: Edward B
authors: EB
authors: Ziff
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D017393:RNA Editing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism; D013570:Synaptic Membranes / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D007473:Ion Channels; D021122:Protein Subunits; D012333:RNA, Messenger; D018091:Receptors, AMPA; D001120:Arginine; C104722:glutamate receptor ionotropic, AMPA 2