Switching heterotrimeric G protein subunits with a chemical dimerizer.

The selective manipulation of single intracellular-signaling events remains one of the key tasks when studying signaling networks. Here, we demonstrate for the first time the stimulation of FKBP fusions of various subunits of heterotrimeric G proteins by the simple addition of the chemical dimerizer rapamycin. Activation of constitutively active Gα(q), but not its GDP-bound form, leads to sustained oscillations of intracellular calcium and myo-inositol 1,4,5-trisphosphate (InsP(3)) levels in HEK cells, independent of the activation of endogenous Gα(q), in full agreement with the InsP(3)-Ca(2+) cross-coupling model of calcium oscillations. Rapamycin-induced translocation of wild-type Gα(s) to the plasma membrane results in elevated cAMP levels. Activation of rapamycin-inducible Gα(s) or Gβ(1)γ(2) evokes extensive modulation of ATP-induced calcium transients. The results demonstrate that inducible heterotrimeric G protein subunits will provide ways for dissecting G protein-coupled receptor signaling.