title: AMPA receptor assembly: atomic determinants and built-in modulators.
abstract: Glutamate-gated ion channels (iGluRs) predominantly operate as heterotetramers to mediate excitatory neurotransmission at glutamatergic synapses. The subunit composition of the receptors determines their targeting to synaptic sites and signalling properties and is therefore a fundamental parameter for neuronal computations. iGluRs assemble as obligatory or preferential heteromers; the mechanisms underlying this selective assembly are only starting to emerge. Here we review recent work in the field and provide an in-depth update on atomic determinants in the assembly domains, which have been facilitated by recent advances in iGluR structural biology. We also discuss the role of alternative RNA processing in the ligand-binding domain, which modulates a central subunit interface and has the capacity to modulate receptor formation in response to external cues. Finally, we review the emerging physiological significance of signalling via distinct iGluR heterotetramers and provide examples of how recruitment of functionally diverse receptors modulates excitatory neurotransmission under physiological and pathological conditions.
authors.affiliation: Laboratory of Cellular and Synaptic MRC LMB and Neurophysiology, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
authors.forename: Madhav
authors.initials: M
authors.lastname: Sukumaran
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Penn
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Greger
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009474:Neurons / Q000502:physiology; D011485:Protein Binding; D055503:Protein Multimerization / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid