Shisa7 is a GABAA receptor auxiliary subunit controlling benzodiazepine actions.
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Piramidales
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Receptores de GABA-A
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Transmisión Sináptica
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Moduladores del GABA
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Diazepam
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Región CA1 Hipocampal
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Proteínas de la Membrana
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Proteínas del Tejido Nervioso
Límite:
Animals
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Humans
Idioma:
En
Revista:
Science
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos