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Publication : Shisa7 is a GABA<sub>A</sub> receptor auxiliary subunit controlling benzodiazepine actions.

First Author  Han W Year  2019
Journal  Science Volume  366
Issue  6462 Pages  246-250
PubMed ID  31601770 Mgi Jnum  J:281687
Mgi Id  MGI:6377643 Doi  10.1126/science.aax5719
Citation  Han W, et al. (2019) Shisa7 is a GABAA receptor auxiliary subunit controlling benzodiazepine actions. Science 366(6462):246-250
abstractText  The function and pharmacology of gamma-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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