Fig. 2. Assembly, maturation and trafficking of GABA_ARs.

GABA_ARs are assembled as pentamers in the ER. This process is primarily regulated by the interaction of the ER-chaperones BiP and calnexin with residues located in the extracellular domain of GABA_AR subunits. Improperly folded and unassembled GABA_AR subunits are targeted for ubiquitination/proteosomal degradation. The ubiquitin-like protein Plic-1 inhibits degradation via interaction with sites located within the intracellular domain of α and β subunits. Plic-1 promotes GABA_AR transport from the ER to the Golgi apparatus. In the Golgi, the palmitoytransferase GODZ palmitoylates a cysteine residue located within the intracellular loop of the γ subunit. Palmitoylation promotes GABA_AR transport through the Golgi towards inhibitory synapses in the cell membrane. The translocation of GABA_AR from the Golgi to the cell surface is believed to be mediated via BIG2 interaction with the intracellular domain of β subunits as well as other regulatory proteins including GABARAP and NSF.