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

• Published in: Journal of neurochemistry 2007-01, Vol.100 (2), p.279-294
• Main Authors: Chen, Zi-Wei, Olsen, Richard W
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - classification; Adaptor Proteins, Signal Transducing - physiology; Aminoacid receptors (glycine, glutamate, gaba); Animals; Biological and medical sciences; Cell receptors; Cell structures and functions; clustering; Fundamental and applied biological sciences. Psychology; GABAA receptor; GABAA receptor associated proteins; Humans; internalization; Membrane Proteins - physiology; Models, Biological; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Protein Structure, Tertiary; Protein Subunits; Receptors, GABA-A - chemistry; Receptors, GABA-A - physiology; trafficking; Two-Hybrid System Techniques; yeast two‐hybrid assay
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04206.x

γ-Aminobutyric acid (GABA), an important inhibitory neurotransmitter in both vertebrates and invertebrates, acts on GABA receptors that are ubiquitously expressed in the CNS. GABAA 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 GABAA receptors plays an important role in regulating GABAA 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 GABAA receptors, for example, the interaction of GABAA 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, GABAA 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 GABAA receptors ranging from enhancing trafficking, to stabilizing surface and internalized receptors, to regulating modification of GABAA receptors. This article reviews the current studies of GABAA receptor intracellular loop-associated proteins.