Shisa7 is a GABA<sub>A</sub> receptor auxiliary subunit controlling benzodiazepine actions.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31601770.
- Also identified by DOI 10.1126/science.aax5719 and PMC identifier 7382361.
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Abstract
The function and pharmacology of γ-aminobutyric acid type A receptors (GABA<sub>A</sub>Rs) 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 GABA<sub>A</sub>Rs. 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 GABA<sub>A</sub>Rs. Genetic deletion of Shisa7 selectively impairs GABAergic transmission and diminishes the effects of diazepam in mice. Our data indicate that Shisa7 regulates GABA<sub>A</sub>R trafficking, function, and pharmacology and reveal a previously unknown molecular interaction that modulates benzodiazepine action in the brain.
Medical subject headings
- CA1 Region, Hippocampal
- Diazepam
- GABA Modulators
- Membrane Proteins
- Nerve Tissue Proteins
- Pyramidal Cells
- Receptors, GABA-A
- Synaptic Transmission