GABAB-receptor subtypes assemble into functional heteromeric complexes

@article{Kaupmann1998GABABreceptorSA,
  title={GABAB-receptor subtypes assemble into functional heteromeric complexes},
  author={K. Kaupmann and B. Malitschek and V. Schuler and J. Heid and W. Froestl and P. Beck and J. Mosbacher and S. Bischoff and {\'A}. Kulik and R. Shigemoto and A. Karschin and B. Bettler},
  journal={Nature},
  year={1998},
  volume={396},
  pages={683-687}
}
B-type receptors for the neurotransmitter GABA (γ-aminobutyric acid) inhibit neuronal activity through G-protein-coupled second-messenger systems, which regulate the release of neurotransmitters and the activity of ion channels and adenylyl cyclase. Physiological and biochemical studies show that there are differences in drug efficiencies at different GABAB receptors, so it is expected that GABAB-receptor (GABABR) subtypes exist. Two GABAB-receptor splice variants have been cloned (GABABR1a and… Expand
Native GABAB receptors are heteromultimers with a family of auxiliary subunits
TLDR
It is shown by functional proteomics that GABAB receptors in the brain are high-molecular-mass complexes of GABAB1, GABAB2 and members of a subfamily of the KCTD (potassium channel tetramerization domain-containing) proteins, established as auxiliary subunits of GABAb receptors that determine the pharmacology and kinetics of the receptor response. Expand
Signal Transduction by GABAB Receptor Heterodimers
TLDR
The interdependent nature of the two subunits for receptor function makes the GABAB receptor a useful model to explore the larger significance of GPCR dimerization for G-protein activation. Expand
Hetero-oligomerization between GABAA and GABAB Receptors Regulates GABAB Receptor Trafficking*
TLDR
Findings reveal that the GABABR1/γ2S interaction results in the regulation of multiple aspects of GABAB receptor trafficking, allowing for cross-talk between these two distinct classes of GABA receptor. Expand
Identification of a GABAB Receptor Subunit, gb2, Required for Functional GABAB Receptor Activity*
TLDR
Characterization of the tissue distribution of each of the receptors by in situhybridization histochemistry in rat brain revealed co-localization of gb1 and gb2 transcripts in many brain regions, suggesting the hypothesis that gb 1 and gB2 may interact in vivo. Expand
Diversity of structure and function of GABAB receptors: a complexity of GABAB-mediated signaling
  • M. Terunuma
  • Chemistry, Medicine
  • Proceedings of the Japan Academy. Series B, Physical and biological sciences
  • 2018
TLDR
The structure, subunit isoforms, and function of GABAB receptors are summarized, including how receptors are localized in specific subcellular compartments, the mechanism regulating cell surface expression and mobility of the receptors, and the diversity of receptor signaling through receptor crosstalk and interacting proteins are discussed. Expand
Heteromeric Assembly of GABABR1 and GABABR2 Receptor Subunits Inhibits Ca2+ Current in Sympathetic Neurons
TLDR
Heteromeric assemblies of GABABR1 and GABABR2 are essential to mediate GABAergic inhibition of Ca2+ channel currents in neurons according to their G-protein-coupled mechanisms. Expand
The GABA receptors
γ-Aminobutyric acid (GABA), an amino acid neurotransmitter, is widely distributed throughout the neuraxis. Two pharmacologically and molecularly distinct GABA receptors have been identified, GABAAExpand
Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants
TLDR
It is demonstrated that GABAB1 isoforms localize to distinct synaptic sites and convey separate functions in vivo, emphasizing molecular differences in synaptic GABAB functions. Expand
Mechanisms of GABA A and GABA B Receptor Gene Regulation and Cell Surface Expression
The γ-aminobutyric acid (GABA) neurotransmitter acting through ionotropic and metabotropic receptor classes exerts the major inhibitory control in the central nervous system. Therapeutic agentsExpand
The heteromeric GABA-B receptor recognizes G-protein α subunit C-termini
TLDR
It is shown that the GABA-BR1 and BR2 subunits form a functional receptor that recognizes the extreme C-termini of the G alpha i and G alpha o proteins when expressed in HEK293 cells, and these findings correspond to data obtained with the mGluR2 receptor, a distant relative of GABA-B proteins. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 31 REFERENCES
Intracellular Retention of Recombinant GABABReceptors*
TLDR
It is reported that recombinant GABAB receptors fail to reach the cell surface when expressed in heterologous systems and are retained in the endoplasmic reticulum when introduced into COS cells and proved that they fail to activate in superior cervical ganglion neurons. Expand
G Protein-Coupled Inwardly Rectifying K+ Channels (GIRKs) Mediate Postsynaptic but Not Presynaptic Transmitter Actions in Hippocampal Neurons
TLDR
It is suggested that a number of G protein-coupled receptors activate the same class of postsynaptic K+ channel, which contains GIRK2, and that the same receptor can couple to different effector systems according to its subcellular location in the neuron. Expand
GABABR1a/R1b‐Type Receptor Antisense Deoxynucleotide Treatment of Melanotropes Blocks Chronic GABAB Receptor Inhibition of High Voltage‐Activated Ca2+ Channels
TLDR
Results show the existence of an R1a/R1b type of GABAB receptor, which, like the D2 receptor, is coupled to chronic HVA‐CC inhibition in melanotropes. Expand
Developmental Changes of Agonist Affinity at GABABR1 Receptor Variants in Rat Brain
TLDR
It is demonstrated that two N-terminal splice variants of the metabotropic receptor for GABA (gamma-amino-butyric acid) were cloned and are identical with GABAB receptors that are photoaffinity labeled with [125I]CGP71872 in rat brain. Expand
Expression cloning of GABAB receptors uncovers similarity to metabotropic glutamate receptors
TLDR
The cloning of GABAB receptors is reported and photoaffinity labelling experiments suggest that the cloned receptors correspond to two highly conserved GABAB receptor forms present in the vertebrate nervous system. Expand
GABAB Receptors
SummaryThe neurotransmitter γ-aminobutyric acid (GABA) activates more than one receptor subtype, including the metabotropic receptor, GABAB. GABAB receptors are located at pre- and postsynaptic sitesExpand
CGP 35348: a centrally active blocker of GABAB receptors.
TLDR
Ionophoretic and behavioural experiments showed that GABAB receptors in the brain were blocked after i.p. administration of CGP 35348, which appeared to be 10-30 times more potent than the GABAB receptor blocker phaclofen. Expand
The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins
TLDR
Sensitive sequence analysis techniques indicate that the metabotropic receptor extracellular domain is similar to bacterial periplasmic amino acid binding proteins, and a structural model built using the observed similarity predicts a ligand-binding site, and mutants with conservative amino acid substitutions at this site are shown to have reduced ligand affinity. Expand
Inhibition of GABAB Receptor Binding by Guanyl Nucleotides
TLDR
GTP and GDP decreased the saturable binding of GABAB to GABAB but not GABAA receptors whereas GMP displayed negligible activity, and the inhibition of ligand binding was the result of a diminished receptor affinity with no change in receptor number. Expand
Defective gamma-aminobutyric acid type B receptor-activated inwardly rectifying K+ currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice.
TLDR
The hypothesis that a nonselective current leads to the weaver phenotype is supported, as the loss of GABAB receptor-activated GIRK current appears coincident with the absence of GirK2 channel protein and the reduction ofGIRK1 channel protein in the Girk2 null mutant mouse, suggesting that GABAB receptors couple to heteromultimers composed of G IRK1 and GIRk2 channel subunits. Expand
...
1
2
3
4
...