title: GARLH Family Proteins Stabilize GABAAReceptors at Synapses.
abstract: Ionotropic neurotransmitter receptors mediate fast synaptic transmission by functioning as ligand-gated ion channels. Fast inhibitory transmission in the brain is mediated mostly by ionotropic GABAAreceptors (GABAARs), but their essential components for synaptic localization remain unknown. Here, we identify putative auxiliary subunits of GABAARs, which we term GARLHs, consisting of LH4 and LH3 proteins. LH4 forms a stable tripartite complex with GABAARs and neuroligin-2 in the brain. Moreover, LH4 is required for the synaptic localization of GABAARs and inhibitory synaptic transmission in the hippocampus. Our findings propose GARLHs as the first identified auxiliary subunits for anion channels. These findings provide new insights into the regulation of inhibitory transmission and the molecular constituents of native anion channels in vivo.
authors.affiliation: Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Tokiwa
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Hoyos-Ramirez
authors.affiliation: Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Martenson
authors.affiliation: Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Megumi
authors.initials: M
authors.lastname: Morimoto-Tomita
authors.affiliation: Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: susumu.tomita@yale.edu.
authors.forename: Susumu
authors.initials: S
authors.lastname: Tomita
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D021122:Protein Subunits; D011963:Receptors, GABA-A