title: Stargazin interacts functionally with the AMPA receptor glutamate-binding module.
abstract: Neuronal AMPA receptors comprise pore forming glutamate receptor (GluR) proteins and auxiliary transmembrane AMPA receptor regulatory (TARP) subunits. TARPs traffic AMPA receptors to synapses and regulate channel gating. Both intracellular and extracellular regions in TARPs regulate AMPA receptors; however, the details for these interactions remain unknown. Here, we employ site-directed mutagenesis to determine functional interactions between GluR1 and the prototypical TARP, stargazin. We find that a point mutation in the glutamate-binding region of GluR1 corresponding to the Lurcher allele of GluRdelta2, abolishes stargazin's effects on receptor trafficking and channel gating. A point mutation that prevents receptor desensitization modulates the effects of stargazin on channel gating but preserves receptor trafficking. These studies identify a functional interaction of stargazin with the extracellular glutamate-binding domain of AMPA receptors.
authors.affiliation: Department of Physiology, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Tomita
authors.forename: Archana
authors.initials: A
authors.lastname: Shenoy
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fukata
authors.forename: Roger A
authors.initials: RA
authors.lastname: Nicoll
authors.forename: David S
authors.initials: DS
authors.lastname: Bredt
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000172:deficiency / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D018091:Receptors, AMPA / Q000235:genetics / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D018698:Glutamic Acid; D009687:Nuclear Proteins; D018091:Receptors, AMPA; C113940:Cacng2 protein, mouse; C413185:TARP