GABAB-receptor subtypes assemble into functional heteromeric complexes

  title={GABAB-receptor subtypes assemble into functional heteromeric complexes},
  author={Klemens Kaupmann and Barbara Malitschek and Valérie Schuler and Jakob Heid and Wolfgang Froestl and Pascal Beck and Johannes Mosbacher and Serge François Bischoff and {\'A}kos Kulik and Ryuichi Shigemoto and Andreas Karschin and Bernhard Bettler},
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… 

Hetero-oligomerization between GABAA and GABAB Receptors Regulates GABAB Receptor Trafficking*

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.

Identification of a GABAB Receptor Subunit, gb2, Required for Functional GABAB Receptor Activity*

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.

Diversity of structure and function of GABAB receptors: a complexity of GABAB-mediated signaling

  • M. Terunuma
  • Biology, Chemistry
    Proceedings of the Japan Academy. Series B, Physical and biological sciences
  • 2018
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.

Mechanisms of GABA A and GABA B Receptor Gene Regulation and Cell Surface Expression

This chapter examines current GABA-R research relevant to the many levels of control over receptor gene regulation and cell surface receptor expression that may be relevant to both health and disease.

Roles of GABAB receptor subtypes in presynaptic auto- and heteroreceptor function regulating GABA and glutamate release

The data suggest that functional GABAB heteroreceptors regulating glutamate release are predominantly, but not exclusively composed of GABAB (1a) and GABAB(2) subunits.



Intracellular Retention of Recombinant GABABReceptors*

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.

GABABR1a/R1b‐Type Receptor Antisense Deoxynucleotide Treatment of Melanotropes Blocks Chronic GABAB Receptor Inhibition of High Voltage‐Activated Ca2+ Channels

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.

Developmental Changes of Agonist Affinity at GABABR1 Receptor Variants in Rat Brain

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.

CGP 35348: a centrally active blocker of GABAB receptors.

Inhibition of GABAB Receptor Binding by Guanyl Nucleotides

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.

Defective gamma-aminobutyric acid type B receptor-activated inwardly rectifying K+ currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice.

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.

Activation of inwardly rectifying K+ channels by GABA‐B receptors expressed in Xenopus oocytes

Findings indicate that GABA-B receptors in the rat cerebellum were functionally expressed in Xenopu s oocytes and activated the cloned GIRKs composed of GirK1 and GIRk2 as heteromultimers.

Subunit Interactions in the Assembly of Neuronal Kir3.0 Inwardly Rectifying K+Channels

Analysis of macroscopic current amplitudes and channel gating kinetics indicated that individual subunits or combinations of Kir3.1 subunits in vivo may not exist due to the spatial conflict of bulky phenylalanines in the pore structure, so a functional comparison with native channels in the CNS was investigated.