Article Figures & Data
Figures
- Fig. 1.
Schematic rendition of a Cys-loop pentameric ligand-gated ion channel receptor. The different shades of gray signify different subunits (unspecified here), assembled in different permutations to generate multiple hetero-oligomers. The purpose of this review is to attempt to list the naturally occurring subtypes of GABAA receptors. Similar chores face those interested in other members of the superfamily as well as other structural types of LGIC. [Adapted from Haefely W (1987) Structure and function of the benzodiazepine receptor. Chimia 41:389–396. Copyright © 1987 Swiss Chemical Society. Used with permission.]
- Fig. 2.
Dendrogram of the known 19 genes for human GABAA receptors. The distances along each line are proportional to the degree of sequence identity between the different homologous subunits. The Greek letters signify subunit families of high (>70%) identity, with different Greek letter subunit families showing homology but lower sequence identity. The distances reflect the evolutionary times required to generate sufficient sequence divergence. [Reproduced from Simon J, Wakimoto H, Fujita N, Lalande M, and Barnard EA (2004) Analysis of the set of GABAA receptor genes in the human genome. J Biol Chem 279:41422–41435. Copyright © 2004. Used with permission.]
Tables
Subunit Gene Chromosome Human Mouse Rat α1 GABRA1 5q34 11 10 α2 GABRA2 4p12 5 14 α3 GABRA3 Xq28 X X α4 GABRA4 4p12 5 14 α5 GABRA5 15q13.2 7 1 α6 GABRA6 5q34 11 10 β1 GABRB1 4p12 5 14 β2 GABRB2 5q34 11 10 β3 GABRB3 15q13.2 7 1 γ1 GABRG1 4p12 5 14 γ2 GABRG2 5q34 11 10 γ3 GABRG3 15q13.2 7 1 δ GARBD 1p36.3 4 5 ϵ GABRE Xq28 X X θ GABRQ Xq28 X X π GABRP 5q35.1 11 10 ρ1 GABRR1 6q15 4 5 ρ2 GABRR2 6q15 4 5 ρ3 GABRR3 3q12.1 16 11 I. Recombinant receptors A. Evidence for their formation, subunit composition, and stoichiometry, using recombinant receptor expression in heterologous cell systems 1. The subunit polypeptides must be shown to be expressed 2. The subunit polypeptides must be shown to coassemble a. Coimmunoprecipitation b. Physical demonstration of subunit interactions by FRET or similar technique c. Formation of pentamers d. Unique subunit arrangement, e.g., using concatemers 3. The corresponding recombinant receptor subtype must be functional B. Evidence for unique properties, including pharmacology 1. Unique biophysical characteristics 2. Unique pharmacology a. Receptor subtype-selective agonists, antagonists, allosteric modulators b. Receptor subtype-selective radioligands c. Potency and efficacy for a series of ligands d. Macrokinetic measures (e.g., apparent EC50 values and binding constants for a series of ligands) II. Native receptors A. Colocalization of subunits 1. Tissue colocalization 2. Cell colocalization (in situ, single-cell RT-PCR) 3. Subcellular colocalization (light and electron microscopy) B. Physical demonstration of subunit interactions (e.g., by coimmunoprecipitation) C. Functional demonstration: 1. Evidence that a given receptor is expressed in real neurons by showing properties (assessed with electrophysiology) corresponding with a recombinant receptor candidate; microscopy may complement 2. Evidence that a given subunit or subunit combination participates in a specific function in vitro or in vivo using genetically modified mice Category A: Identified α1β2γ2 α2βγ2 α3βγ2 α4βγ2 α4β2δ α4β3δ α5βγ2 α6βγ2 α6β2δ α6β3δ ρ Category B: Existence with high probability α1β3γ2 α1βδ α5β3γ2 αβ1γ/αβ1δ αβ α1α6βγ/α1α6βδ Category C: Tentative ρ1 ρ2 ρ3 αβγ1 αβγ3 αβθ αβϵ αβπ αxαyβγ2
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