title: α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors adopt different subunit arrangements.
abstract: Ionotropic glutamate receptors are widely distributed in the central nervous system and play a major role in excitatory synaptic transmission. All three ionotropic glutamate subfamilies (i.e. AMPA-type, kainate-type, and NMDA-type) assemble as tetramers of four homologous subunits. There is good evidence that both heteromeric AMPA and kainate receptors have a 2:2 subunit stoichiometry and an alternating subunit arrangement. Recent studies based on presumed structural homology have indicated that NMDA receptors adopt the same arrangement. Here, we use atomic force microscopy imaging of receptor-antibody complexes to show that whereas the GluA1/GluA2 AMPA receptor assembles with an alternating (i.e. 1/2/1/2) subunit arrangement, the GluN1/GluN2A NMDA receptor adopts an adjacent (i.e. 1/1/2/2) arrangement. We conclude that the two types of ionotropic glutamate receptor are built in different ways from their constituent subunits. This surprising finding necessitates a reassessment of the assembly of these important receptors.
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
authors.forename: Dilshan
authors.initials: D
authors.lastname: Balasuriya
authors.forename: Tom A
authors.initials: TA
authors.lastname: Goetze
authors.forename: Nelson P
authors.initials: NP
authors.lastname: Barrera
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Stewart
authors.forename: Yuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: J Michael
authors.initials: JM
authors.lastname: Edwardson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006801:Humans; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C104722:glutamate receptor ionotropic, AMPA 2
keywords: Atomic Force Microscopy; Cell Surface Receptor; Glutamate Receptors, Ionotropic (AMPA, NMDA); Protein Complexes; Single-particle Analysis