GB1a

GB1a is an isoform of the GABA-B receptor subunit 1 (GB1), encoded by the GABBR1 gene and produced by alternative splicing. Compared with the GB1b isoform, GB1a contains an additional N-terminal region with two sushi domains, a feature that influences receptor trafficking and localization in neurons. GB1a participates in GABA-B receptor signaling in the brain, typically forming a heterodimer with the GABA-B receptor subunit 2 (GB2) to produce a functional receptor.

The GB1/GB2 heterodimer is a member of the class C G protein-coupled receptor family. GB2 is required for proper transport to the plasma membrane and for coupling to Gi/o proteins, whereas GB1a contributes the extracellular ligand-binding domain and influences subcellular targeting through its sushi motifs. Expression of GB1a is prominent in several brain regions, including the hippocampus and cerebral cortex, with GB1b showing a somewhat different distribution.

Functionally, GABA-B receptors modulate synaptic activity by inhibiting adenylyl cyclase, reducing cAMP formation, suppressing voltage-gated calcium channels, and activating G protein-gated inwardly rectifying potassium (GIRK) channels. This leads to decreased neurotransmitter release and neuronal excitability, with both pre- and postsynaptic effects depending on localization.

Pharmacologically, baclofen is a clinically used GABA-B receptor agonist for treating spasticity; research continues into positive allosteric modulators and potential isoform-selective ligands to refine therapeutic options for pain, anxiety, and addiction.