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Shisa7 is a GABAA receptor auxiliary subunit controlling benzodiazepine actions.
Han, Wenyan; Li, Jun; Pelkey, Kenneth A; Pandey, Saurabh; Chen, Xiumin; Wang, Ya-Xian; Wu, Kunwei; Ge, Lihao; Li, Tianming; Castellano, David; Liu, Chengyu; Wu, Ling-Gang; Petralia, Ronald S; Lynch, Joseph W; McBain, Chris J; Lu, Wei.
Afiliación
  • Han W; Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
  • Li J; Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
  • Pelkey KA; Cellular and Synaptic Neuroscience Section, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • Pandey S; Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chen X; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
  • Wang YX; Advanced Imaging Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wu K; Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ge L; Synaptic Transmission Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
  • Li T; Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
  • Castellano D; Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
  • Liu C; Transgenetic Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wu LG; Synaptic Transmission Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
  • Petralia RS; Advanced Imaging Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lynch JW; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
  • McBain CJ; Cellular and Synaptic Neuroscience Section, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lu W; Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. luw4@mail.nih.gov.
Science ; 366(6462): 246-250, 2019 10 11.
Article en En | MEDLINE | ID: mdl-31601770
ABSTRACT
The function and pharmacology of γ-aminobutyric acid type A receptors (GABAARs) are of great physiological and clinical importance and have long been thought to be determined by the channel pore-forming subunits. We discovered that Shisa7, a single-passing transmembrane protein, localizes at GABAergic inhibitory synapses and interacts with GABAARs. Shisa7 controls receptor abundance at synapses and speeds up the channel deactivation kinetics. Shisa7 also potently enhances the action of diazepam, a classic benzodiazepine, on GABAARs. Genetic deletion of Shisa7 selectively impairs GABAergic transmission and diminishes the effects of diazepam in mice. Our data indicate that Shisa7 regulates GABAAR trafficking, function, and pharmacology and reveal a previously unknown molecular interaction that modulates benzodiazepine action in the brain.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células Piramidales / Receptores de GABA-A / Transmisión Sináptica / Moduladores del GABA / Diazepam / Región CA1 Hipocampal / Proteínas de la Membrana / Proteínas del Tejido Nervioso Límite: Animals / Humans Idioma: En Revista: Science Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células Piramidales / Receptores de GABA-A / Transmisión Sináptica / Moduladores del GABA / Diazepam / Región CA1 Hipocampal / Proteínas de la Membrana / Proteínas del Tejido Nervioso Límite: Animals / Humans Idioma: En Revista: Science Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos