Phylogenetic Comparison of the Photoaffinity‐Labeled Benzodiazepine Receptor Subunits

Hebebrand, Johannes; Friedl, Waltraut; Breidenbach, Bernd; Propping, Peter

doi:10.1111/j.1471-4159.1987.tb05633.x

Cited by 52 publications

(28 citation statements)

References 19 publications

(23 reference statements)

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“…As previously found [24], [25], [38], the presence of putative GABA α-, β- and ρ-like receptor subunits in the genome of C. intestinalis support that this ancestral duplication most likely occurred before the divergence of urochordates. These results suggest that benzodiazepine sensitivity evolved early, in marked contrast to previous proposals [39], [40]. In line with our finding, recent electrophysiological data suggest that invertebrates (e.g., Hydra vulgaris ) are responsive to benzodiazepine modulation and this response is similar to the response to GABA [41].…”

Section: Discussionsupporting

confidence: 88%

Early Evolution of Ionotropic GABA Receptors and Selective Regimes Acting on the Mammalian-Specific Theta and Epsilon Subunits

et al. 2007

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BackgroundThe amino acid neurotransmitter GABA is abundant in the central nervous system (CNS) of both invertebrates and vertebrates. Receptors of this neurotransmitter play a key role in important processes such as learning and memory. Yet, little is known about the mode and tempo of evolution of the receptors of this neurotransmitter. Here, we investigate the phylogenetic relationships of GABA receptor subunits across the chordates and detail their mode of evolution among mammals.Principal FindingsOur analyses support two major monophyletic clades: one clade containing GABAA receptor α, γ, and ε subunits, and another one containing GABAA receptor ρ, β, δ, θ, and π subunits. The presence of GABA receptor subunits from each of the major clades in the Ciona intestinalis genome suggests that these ancestral duplication events occurred before the divergence of urochordates. However, while gene divergence proceeded at similar rates on most receptor subunits, we show that the mammalian-specific subunits θ and ε experienced an episode of positive selection and of relaxed constraints, respectively, after the duplication event. Sites putatively under positive selection are placed on a three-dimensional model obtained by homology-modeling.ConclusionsOur results suggest an early divergence of the GABA receptor subunits, before the split from urochordates. We show that functional changes occurred in the lineages leading to the mammalian-specific subunit θ, and we identify the amino acid sites putatively responsible for the functional divergence. We discuss potential consequences for the evolution of mammals and of their CNS.

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Section: Discussionsupporting

confidence: 88%

Early Evolution of Ionotropic GABA Receptors and Selective Regimes Acting on the Mammalian-Specific Theta and Epsilon Subunits

et al. 2007

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“…A comparison among mammalian, amphibian, and fish brains demonstrated that a common protein with molecular mass of -5 1 kDa is intensely photoaffinity labeled by [3H]Flu in most species studied of mammals, birds, amphibians, and reptiles, except fish, where a 55-kDa protein is labeled instead (Hebebrand et al, 1986(Hebebrand et al, , 1987. Insects show two bands at 46 and 59 kDa photolabeled by [3H]Flu; their relationship to mammalian GABAA receptors is unclear (Robinson et al, 1986).…”

Section: Phylogeny and Ontogeny Of Bz Receptorsmentioning

confidence: 99%

“…This ligand labels a 50 to 52 kDa polypeptide band in mammalian brain (Mohler et al, 1980), although additional minor species of higher molecular mass are detectable in some brain regions (Sieghart et al, 1983;Fuchs and Sieghart, 1989;Bureau and Olsen, 1990). A phylogenetic study revealed that a major labeled polypeptide of the same molecular mass (51 kDa) was present in brain from tetrapods, amphibians, and the primitive lungfish (Hebebrand et al, 1986(Hebebrand et al, , 1987. Additional labeled polypeptides were detected in several species of reptiles, birds, and mammals, suggesting an isoreceptor complex arising by gene duplication and subsequent divergence (Hebebrand et al, 1987).…”

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confidence: 99%

“…A phylogenetic study revealed that a major labeled polypeptide of the same molecular mass (51 kDa) was present in brain from tetrapods, amphibians, and the primitive lungfish (Hebebrand et al, 1986(Hebebrand et al, , 1987. Additional labeled polypeptides were detected in several species of reptiles, birds, and mammals, suggesting an isoreceptor complex arising by gene duplication and subsequent divergence (Hebebrand et al, 1987). Indeed, multiple GABA-BZ receptor polypeptides have now been cloned and constitute a gene family (Levitan et al, 1988).…”

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confidence: 99%

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Pharmacological and Biochemical Properties of the γ‐Aminobutyric Acid–Benzodiazepine Receptor Protein from Codfish Brain

Deng¹,

Nielsen²,

Olsen³

1991

Journal of Neurochemistry

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The gamma-aminobutyric acidA (GABAA) receptor of codfish brain has been purified to homogeneity and contains a single polypeptide band of 56 kDa molecular mass. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS-PAGE) of codfish GABA receptor photoaffinity-labeled by both [3H]flunitrazepam ([3H]Flu) and [3H]muscimol showed a single radioactive peak with molecular mass of 56 kDa, in contrast to the multiple subunits found in other vertebrate species. The codfish receptor, purified using benzodiazepine (BZ, Ro 7-1986/1) affinity chromatography, contains an apparent single band both by isoelectric focussing and on a silver-stained SDS gel. The receptor density and affinity constants for [3H]muscimol and [3H]Flu binding are comparable to those in mammalian brain, and the specific activity (greater than 1,000 pmol/mg of protein) is comparable to that of preparations purified from those sources. The pharmacological specificity of the codfish GABA-BZ receptor is generally similar to that of mammalian brain, including GABA-BZ coupling. The BZ binding exhibits homogeneous kinetic properties resembling those of the mammalian BZ2 receptor type, and shows strong GABA enhancement of [3H]Flu binding and weaker pentobarbital potentiation. This is consistent with other observations of an earlier phylogenetic, as well as ontogenetic, emergence in mammals of the BZ2 receptor subtype than the BZ1. Codfish GABA receptor is postulated to be a homo-oligomer in which the conformation of GABA and BZ recognition sites is very similar to that in the mammalian hetero-oligomeric GABAA receptor. The codfish receptor appears to be encoded by an ancestral gene and indicates an early development of BZ-GABA coupling.

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“…Photoaffinity labeling experiments with [3H]flunitrazepam ([3H]FNZ) have indicated that the asubunit carries the benzodiazepine (BZ) binding site (Mohler et al, 1980). Photoaffinity labeling of crude synaptic membranes with [3H]FNZ followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorography revealed regional as well as species variations of the M, values of the BZ binding proteins (Sieghart and Karobath, 1980;Hebebrand et al, 1987). Species variation and regional heterogeneity of the M, values of the BZ binding proteins persisted after deglycosylation with endoglycosidase F (Endo F) .…”

mentioning

confidence: 99%

Postmortem Degradation Alters Fluorographic Labeling Patterns and Affinities of Benzodiazepine Binding Proteins

Reichelt¹,

Schmitz

1989

Journal of Neurochemistry

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To investigate the effect of endogenous proteolysis on the molecular weights of the benzodiazepine binding proteins, brains of trout, chicken, and rat were removed immediately after death and stored at room temperature for various periods of time before they were frozen. Photoaffinity labeling of membranes with [3H]flunitrazepam, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography, revealed proteolytic fragments of 47K in trout, chicken, and rat. The proteolysis set in rapidly after death. Seemingly in parallel with the degradation observed fluorographically, the affinity for [3H]flunitrazepam increased without systematic changes in receptor density. The degradation pattern was not identical to that of the photolabeled trypsinized benzodiazepine binding proteins. The endogenous proteolytic fragments were deglycosylated in two steps. In conclusion, proteolytic effects must be taken into account when interpreting labeling patterns and binding parameters.

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Phylogenetic Comparison of the Photoaffinity‐Labeled Benzodiazepine Receptor Subunits

Cited by 52 publications

References 19 publications

Early Evolution of Ionotropic GABA Receptors and Selective Regimes Acting on the Mammalian-Specific Theta and Epsilon Subunits

Early Evolution of Ionotropic GABA Receptors and Selective Regimes Acting on the Mammalian-Specific Theta and Epsilon Subunits

Pharmacological and Biochemical Properties of the γ‐Aminobutyric Acid–Benzodiazepine Receptor Protein from Codfish Brain

Postmortem Degradation Alters Fluorographic Labeling Patterns and Affinities of Benzodiazepine Binding Proteins

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