GABAB Receptor (Ser923), R1-Subunit (GABBR1) Antibody – Rabbit Polyclonal

Function: Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. 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. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. 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. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception. Ref.1

Subunit structure: Heterodimer of GABBR1 and GABBR2. Homodimers may form, but are inactive. Interacts with the leucine zipper of the C-terminal bZIP domain of ATF4 via its C-terminal region. Interacts with JAKMIP1. Ref.4 Ref.6 Ref.7 Ref.9

Subcellular location: Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein. Cell projection › dendrite. Note: Coexpression of GABBR1 and GABBR2 is required for GABBR1 maturation and transport to the plasma membrane. Colocalizes with ATF4 in hippocampal neuron dendritic membranes. Ref.1 Ref.7

Tissue specificity: Isoform 1A, isoform 1B and isoform 1C are expressed in testis, stomach, spinal cord and brain including cerebral cortical layers, pyramidal cell layers of the hippocampus, granular cell layers of the dentate gyrus, basal ganglia, cerebellum (predominantly in Purkinje cells followed by granular layer). Isoform 1B is also expressed in kidney and liver. Isoform 1D is expressed in forebrain, cerebellum, eye, kidney, and urinary bladder. Ref.1 Ref.2 Ref.5

Domain: Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABA-B receptor 2. The linker region between the transmembrane domain 3 (TM3) and the transmembrane domain 4 (TM4) probably play a role in the specificity for G-protein coupling.

Sequence similarities: Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.Contains 2 Sushi (CCP/SCR) domains.