The brefeldin A‐inhibited GDP/GTP exchange factor 2, a protein involved in vesicular trafficking, interacts with the β subunits of the GABAA receptors

We have found that the brefeldin A‐inhibited GDP/GTP exchange factor 2 (BIG2) interacts with the β subunits of the γ‐aminobutyric acid type‐A receptor (GABAAR). BIG2 is a Sec7 domain‐containing guanine nucleotide exchange factor known to be involved in vesicular and protein trafficking. The interaction between the 110 amino acid C‐terminal fragment of BIG2 and the large intracellular loop of the GABAAR β subunits was revealed with a yeast two‐hybrid assay. The native BIG2 and GABAARs interact in the brain since both coprecipitated from detergent extracts with either anti‐GABAAR or anti‐BIG2 antibodies. In transfected human embryonic kidney cell line 293 cells, BIG2 promotes the exit of GABAARs from endoplasmic reticulum. Double label immunofluorescence of cultured hippocampal neurons and electron microscopy immunocytochemistry of rat brain tissue show that BIG2 concentrates in the trans‐Golgi network. BIG2 is also present in vesicle‐like structures in the dendritic cytoplasm, sometimes colocalizing with GABAARs. BIG2 is present in both inhibitory GABAergic synapses that contain GABAARs and in asymmetric excitatory synapses. The results are consistent with the hypotheses that the interaction of BIG2 with the GABAAR β subunits plays a role in the exocytosis and trafficking of assembled GABAAR to the cell surface.