GABBR1

This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined.

Full Name

gamma-aminobutyric acid type B receptor subunit 1

Function

Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:9872316, PubMed:9872744, PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054).

Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688).

Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10906333, PubMed:10773016, PubMed:10075644, PubMed:9872744, PubMed:24305054).

Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644).

Calcium is required for high affinity binding to GABA (By similarity).

Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:9844003).

Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:9844003, PubMed:9872316, PubMed:10075644, PubMed:9872744, PubMed:22660477).

Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable). Activated by (-)-baclofen, cgp27492 and blocked by phaclofen (PubMed:9844003, PubMed:9872316, PubMed:24305054).

Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.

Biological Process

Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway Source: UniProtKB
Gamma-aminobutyric acid signaling pathway Source: UniProtKB
Neuron-glial cell signaling Source: ARUK-UCL

Cellular Location

Cell membrane; Postsynaptic cell membrane; Dendrite. Colocalizes with ATF4 in hippocampal neuron dendritic membranes (By similarity). Coexpression of GABBR1 and GABBR2 is required for GABBR1 maturation and transport to the plasma membrane (PubMed:15617512).
Isoform 1E: Secreted

Topology

Extracellular: 15-591
Helical: 592-612
Cytoplasmic: 613-631
Helical: 632-652
Extracellular: 653-667
Helical: 668-688
Cytoplasmic: 689-710
Helical: 711-731
Extracellular: 732-768
Helical: 769-789
Cytoplasmic: 790-804
Helical: 805-825
Extracellular: 826-833
Helical: 834-854
Cytoplasmic: 855-961