Shisa7 is a GABA Receptor Auxiliary Subunit Controlling Benzodiazepine Actions

Overview

Journal Science

Specialty Science

Date 2019 Oct 12

PMID 31601770

Citations 45

Authors

Wenyan Han

Jun Li

Kenneth A Pelkey

Saurabh Pandey

Xiumin Chen

Ya-Xian Wang

Kunwei Wu

Lihao Ge

Tianming Li

David Castellano

Chengyu Liu

Ling-Gang Wu

Ronald S Petralia

Joseph W Lynch

Chris J McBain

Wei Lu

Affiliations

Soon will be listed here.

Abstract

The function and pharmacology of γ-aminobutyric acid type A receptors (GABARs) 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 GABARs. 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 GABARs. Genetic deletion of Shisa7 selectively impairs GABAergic transmission and diminishes the effects of diazepam in mice. Our data indicate that Shisa7 regulates GABAR trafficking, function, and pharmacology and reveal a previously unknown molecular interaction that modulates benzodiazepine action in the brain.

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