title: Distinct functions of kainate receptors in the brain are determined by the auxiliary subunit Neto1.
abstract: Ionotropic glutamate receptors principally mediate fast excitatory transmission in the brain. Among the three classes of ionotropic glutamate receptors, kainate receptors (KARs) have a unique brain distribution, which has been historically defined by (3)H-radiolabeled kainate binding. Compared with recombinant KARs expressed in heterologous cells, synaptic KARs exhibit characteristically slow rise-time and decay kinetics. However, the mechanisms responsible for these distinct KAR properties remain unclear. We found that both the high-affinity binding pattern in the mouse brain and the channel properties of native KARs are determined by the KAR auxiliary subunit Neto1. Through modulation of agonist binding affinity and off-kinetics of KARs, but not trafficking of KARs, Neto1 determined both the KAR high-affinity binding pattern and the distinctively slow kinetics of postsynaptic KARs. By regulating KAR excitatory postsynaptic current kinetics, Neto1 can control synaptic temporal summation, spike generation and fidelity.
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Straub
authors.forename: David L
authors.initials: DL
authors.lastname: Hunt
authors.forename: Miwako
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Kwang S
authors.initials: KS
authors.lastname: Kim
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Castillo
authors.forename: Susumu
authors.initials: S
authors.lastname: Tomita
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D055592:Biophysical Phenomena / Q000187:drug effects / Q000235:genetics; D001703:Biophysics; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism*; D002461:Cell Line, Transformed; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000493:pharmacokinetics / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D051528:Guanylate Kinases; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007608:Kainic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D026502:LDL-Receptor Related Proteins; D008077:Lipoproteins, LDL / Q000172:deficiency / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000145:classification / Q000172:deficiency / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D000076122:Disks Large Homolog 4 Protein; D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D007608:Kainic Acid; D026502:LDL-Receptor Related Proteins; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D021122:Protein Subunits; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; D014316:Tritium; C501447:Dlg4 protein, mouse; C539204:NETO2 protein, mouse; C486748:Neto1 protein, mouse