Molecular diversity, trafficking and subcellular localization of GABAB receptors

Pharmacology & Therapeutics
B Bettler, Jim Yu-Hsiang Tiao

Abstract

GABAB receptors are the G-protein coupled receptors for the main inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA). While native studies predicted pharmacologically distinct GABAB receptor subtypes, molecular studies failed to identify the expected receptor varieties. Mouse genetic experiments therefore addressed whether the cloned receptors can account for the classical electrophysiological, biochemical and behavioral GABAB responses or whether additional receptors exist. Among G-protein coupled receptors, GABAB receptors are unique in that they require 2 distinct subunits for functioning. This atypical receptor structure triggered a large body of work that investigated the regulation of receptor assembly and trafficking. With the availability of molecular tools, substantial progress was also made in the analysis of the receptor protein distribution in neuronal compartments. Here, we review recent studies that shed light on the molecular diversity, the subcellular distribution and the cell surface dynamics of GABAB receptors.

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