GABAA receptor associated proteins: a key factor regulating GABAA receptor function

Abstract

γ‐Aminobutyric acid (GABA), an important inhibitory neurotransmitter in both vertebrates and invertebrates, acts on GABA receptors that are ubiquitously expressed in the CNS. GABA A receptors also represent a major site of action of clinically relevant drugs, such as benzodiazepines, barbiturates, ethanol, and general anesthetics. It has been shown that the intracellular M3‐M4 loop of GABA A receptors plays an important role in regulating GABA A receptor function. Therefore, studies of the function of receptor intracellular loop associated proteins become important for understanding mechanisms of regulating receptor activity. Recently, several labs have used the yeast two‐hybrid assay to identify proteins interacting with GABA A receptors, for example, the interaction of GABA A receptor associated protein (GABARAP) and Golgi‐specific DHHC zinc finger protein (GODZ) with γ subunits, PRIP, phospholipase C‐related, catalytically inactive proteins (PRIP‐1) and (PRIP‐2) with GABARAP and receptor γ2 and β subunits, Plic‐1 with some α and β subunits, radixin with the α5 subunit, HAP1 with the β1 subunit, GABA A receptor interacting factor‐1 (GRIF‐1) with the β2 subunit, and brefeldin A‐inhibited GDP/GTP exchange factor 2 (BIG2) with the β3 subunit. These proteins have been shown to play important roles in modulating the activities of GABA A receptors ranging from enhancing trafficking, to stabilizing surface and internalized receptors, to regulating modification of GABA A receptors. This article reviews the current studies of GABA A receptor intracellular loop‐associated proteins.