GB1b

GB1b is an isoform of the GABA-B receptor subunit 1 (GB1) produced by alternative splicing of the GABBR1 gene. Unlike the GB1a isoform, GB1b lacks the N-terminal region containing sushi-domain–type sequences, resulting in a shorter extracellular N-terminus. Both GB1a and GB1b can form heterodimers with the GABA-B receptor subunit GB2 to create functional GABA-B receptor complexes.

GB1b comprises the ligand-binding sites and other conserved regions necessary for receptor maturation and trafficking, but its truncated N-terminus leads to distinct subcellular localization and trafficking properties compared with GB1a-containing receptors. When paired with GB2, GB1b-containing receptors are capable of responding to GABA and other agonists, enabling G-protein signaling despite the absence of the longer N-terminal domain found in GB1a.

Functionally, GABA-B receptors are metabotropic, coupling to Gi/o proteins to inhibit adenylyl cyclase, modulate calcium and potassium channels, and reduce neurotransmitter release. Activation of GB1b/GB2 receptors by GABA or agonists can decrease neuronal excitability and modulate synaptic transmission, contributing to the inhibitory control exerted by GABA-B signaling.

Expression studies indicate GB1b transcripts are present in multiple brain regions, including cortex and hippocampus, aligning with roles in regulating network activity. Clinically, GABA-B receptors are targets of baclofen, a therapeutic agonist used to treat spasticity, while the specific contributions of GB1b isoforms to disease mechanisms remain an area of active research.