title: Stargazin Modulation of AMPA Receptors.
abstract: Fast excitatory synaptic signaling in the mammalian brain is mediated by AMPA-type ionotropic glutamate receptors. In neurons, AMPA receptors co-assemble with auxiliary proteins, such as stargazin, which can markedly alter receptor trafficking and gating. Here, we used luminescence resonance energy transfer measurements to map distances between the full-length, functional AMPA receptor and stargazin expressed in HEK293 cells and to determine the ensemble structural changes in the receptor due to stargazin. In addition, we used single-molecule fluorescence resonance energy transfer to study the structural and conformational distribution of the receptor and how this distribution is affected by stargazin. Our nanopositioning data place stargazin below the AMPA receptor ligand-binding domain, where it is well poised to act as a scaffold to facilitate the long-range conformational selection observations seen in single-molecule experiments. These data support a model of stargazin acting to stabilize or select conformational states that favor activation.
authors.affiliation: Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Sana A
authors.initials: SA
authors.lastname: Shaikh
authors.affiliation: Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Biochemistry and Molecular Biology Graduate Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Drew M
authors.initials: DM
authors.lastname: Dolino
authors.affiliation: Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Garam
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Rice University, Houston, TX 77251, USA.
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: MacLean
authors.affiliation: Department of Chemistry, Rice University, Houston, TX 77251, USA; Applied Physics Graduate Program, Rice University, Houston, TX 77251, USA.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Flatebo
authors.affiliation: Department of Chemistry, Rice University, Houston, TX 77251, USA; Department of Electrical and Computer Engineering, Rice University, Houston, TX 77251, USA; Applied Physics Graduate Program, Rice University, Houston, TX 77251, USA.
authors.forename: Christy F
authors.initials: CF
authors.lastname: Landes
authors.affiliation: Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Biochemistry and Molecular Biology Graduate Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: vasanthi.jayaraman@uth.tmc.edu.
authors.forename: Vasanthi
authors.initials: V
authors.lastname: Jayaraman
mesh_terms: D015220:Calcium Channels / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
chemical_list: C491912:CACNG2 protein, human; D015220:Calcium Channels; D008024:Ligands; D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
keywords: AMPA receptor modulation; AMPA receptors; desensitized state; smFRET; stargazin; transmembrane AMPA receptor regulatory proteins