title: Mutation of a glutamate receptor motif reveals its role in gating and delta2 receptor channel properties.
abstract: Despite its importance in the cerebellum, the functions of the orphan glutamate receptor delta2 are unknown. We examined a mutant delta2 receptor channel in lurcher mice that was constitutively active in the absence of ligand. Because this mutation was within a highly conserved motif (YTANLAAF), we tested its effect on several glutamate receptors. Mutant delta2 receptors showed distinct channel properties, including double rectification of the current-voltage relationship, sensitivity to a polyamine antagonist and moderate Ca 2+ permeability, whereas other constitutively active mutant glutamate channels resembled wild-type channels in these respects. Moreover, the kinetics of ligand-activated currents were strikingly altered. We conclude that the delta2 receptor has a functional ion channel pore similar to that of glutamate receptors. The motif may have a role in the channel gating of glutamate receptors.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kohda
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Yuzaki
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001569:Benzodiazepines; D001581:Benzothiadiazines / Q000494:pharmacology; D002460:Cell Line; D017124:Conserved Sequence; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics*; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000737:chemistry / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
chemical_list: D014151:Anti-Anxiety Agents; D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009467:Neuromuscular Depolarizing Agents; D011810:Quinoxalines; D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C012301:domoic acid; C004639:cyclothiazide; D007608:Kainic Acid