GABA-B1 Receptors are Coupled to the ERK1/2 MAP Kinase Pathway in the Absence of GABA-B2 Subunits

In the current model of γ-aminobutyric acid (GABA) B receptor function, there is a requirement for GABA-B 1/2 heterodimerisation for targetting to the cell surface. However, different lines of evidence suggest that the GABA-B 1 subunit can form a functional receptor in the absence of GABA-B 2 . We observed coupling of endogenous GABA-B 1 receptors in the DI-TNC1 glial cell line to the ERK pathway in response to baclofen even though these cells do not express GABA-B 2 . GABA-B 1A receptors were also able to mediate a rapid, transient, and dose-dependent activation of the ERK1/2 MAP kinase pathway when transfected alone into HEK 293 cells. The response was abolished by G i/o and MEK inhibition, potentiated by inhibitors of phospholipase C and protein kinase C and did not involve PI-3-kinase activity. Finally, using bioluminescence resonance energy transfer and co-immunoprecipitation, we show the existence of homodimeric GABA-B 1A receptors in transfected HEK293 cells. Altogether, our observations show that GABA-B 1A receptors are able to activate the ERK1/2 pathway despite the absence of surface targetting partner GABA-B 2 in both HEK 293 cells and the DI-TNC1 cell line.