The Organizing Principle of GABA Receptor Complexes: Physiological and Pharmacological Implications

Overview

Journal Basic Clin Pharmacol Toxicol

Specialties Pharmacology
Toxicology

Date 2019 Apr 30

PMID 31033219

Citations 18

Authors

Thorsten Fritzius

Bernhard Bettler

Affiliations

Soon will be listed here.

Abstract

GABA receptors (GBRs), the G protein-coupled receptors for the neurotransmitter γ-aminobutyric acid (GABA), regulate synaptic transmission at most synapses in the brain. Proteomic approaches revealed that native GBR complexes assemble from an inventory of ~30 proteins that provide a molecular basis for the functional diversity observed with these receptors. Studies with reconstituted GBR complexes in heterologous cells and complementary knockout studies have allowed to identify cellular and physiological functions for obligate and several non-obligate receptor components. It emerges that modular association of receptor components in space and time generates a variety of multiprotein receptor complexes with different localizations, kinetic properties and effector channels. This article summarizes current knowledge on the organizing principle of GBR complexes. We further discuss unanticipated receptor functions, links to disease and opportunities for drug discovery arising from the identification of novel receptor components.

Citing Articles

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Role of Rab10 in cocaine-induced behavioral effects is associated with GABAB receptor membrane expression in the nucleus accumbens.

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Synaptotagmin-11 facilitates assembly of a presynaptic signaling complex in post-Golgi cargo vesicles.

Trovo L, Kouvaros S, Schwenk J, Fernandez-Fernandez D, Fritzius T, Rem P EMBO Rep. 2024; 25(6):2610-2634.

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