Figure 2. Trafficking of GABA_A receptors.

GABA_A receptor subunits are synthesized and assembled into pentameric structures in the endoplasmic reticulum (ER). This process is carefully regulated in the ER. The fate of GABA_A receptor subunits can be modulated by ubiquitination and subsequent ER-associated degradation via the proteasome. Ubiquitinated GABA_A receptor subunits can also be modulated via their association with Plic-1. Plic-1 facilitates GABA_A receptor accumulation at the synapse by preventing the degradation of ubiquitinated GABA_A receptors. Exit into the Golgi network and subsequent trafficking to the plasma membrane are also facilitiated by a number of GABA_A receptor-associated proteins. GABARAP associates with the γ2 subunit of GABA_A receptors and aids in the trafficking of receptors from the Golgi network to the plasma membrane. NSF and BIG2 are also localized to the Golgi network, where they bind to β subunits of GABA_A receptors and modulate receptor trafficking. Palmitoylation of γ subunits occurs in the Golgi apparatus as a result of an association with the palmitoyltransferase, GODZ, and is a critical step in the delivery of GABA_A receptors to the plasma membrane. GRIF proteins play a role in the trafficking of GABA_A receptors to the membrane. PRIP proteins also play essential roles in the trafficking of GABA_A receptors, as well as in modulating the phosphorylation state of GABA_A receptors.