title: Functional Roles of the Edited Isoform of GluA2 in GluA2-Containing AMPA Receptor Channels.
abstract: GluA2R is the edited isoform at the Q/R site of the AMPA receptor GluA2 subunit. In vivo, GluA2R assembles with other AMPA receptor subunits into a high-conductance, tetrameric complex. Here we study the functional role of GluA2R in the context of GluA1/2R and GluA2Q/2R heteromeric receptors, using whole-cell recording and a laser-pulse photolysis technique. We find the incorporation of GluA2R with GluA1 or GluA2Q slows the channel-opening and channel-closing rates; for GluA2Q/2R, it further lowers EC50, compared to the value of the GluA2Q homomeric channels. When a conserved leucine-to-tyrosine (L → Y) mutation is "placed" in each of these subunits, the L → Y mutation exhibits a greater effect in GluA2R than in GluA1. Together, our results show GluA2R is the dominating isoform that shapes the overall functional properties of the GluA2R-containing channels. Our results further suggest that glutamate most likely binds to GluA2R with an EC50of ∼0.5 mM, rather than a non-GluA2R subunit in a heteromeric AMPA receptor, and binding of two glutamate molecules to the two GluA2R subunits is sufficient to initiate a conformational change, leading to the opening of the channel.
authors.affiliation: Department of Chemistry and Center for Neuroscience Research, University at Albany, State University of New York , Albany, New York 12222, United Stated.
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Chemistry and Center for Neuroscience Research, University at Albany, State University of New York , Albany, New York 12222, United Stated.
authors.forename: Chi-Yen
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Chemistry and Center for Neuroscience Research, University at Albany, State University of New York , Albany, New York 12222, United Stated.
authors.forename: Li
authors.identifier: 0000-0002-0917-9663
authors.initials: L
authors.lastname: Niu
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D009154:Mutation; D018408:Patch-Clamp Techniques; D010782:Photolysis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018698:Glutamic Acid; D020033:Protein Isoforms; D021122:Protein Subunits; D018091:Receptors, AMPA; D011994:Recombinant Proteins; C104722:glutamate receptor ionotropic, AMPA 2