Over half of all drug targets are so-called G-protein coupled receptors (GPCR). However, measuring the variety of intracellular events that GPCRs evoke requires sophisticated techniques that do not readily lend themselves to high-throughput screening. Johns Hopkins researchers have therefore created fluorescently labeled GPCRs to throw light on this problem (Science 291, 2408–2411, 2001). GPCRs are formed from a complex of α-, β-, and γ-subunits, embedded within the membrane and extending into the cell's interior. When a drug, hormone, or neurotransmitter binds to the receptor, the subunits break apart. To catch these subunits in the act of separation, Chris Janetopoulos and colleagues tagged α- and β-subunits with cyan and yellow fluorescent labels, respectively. The close proximity of the subunits, and thus of the fluorescent labels, results in so-called fluorescence resonance energy transfer (FRET), and the GPCR complex glows yellow. When the subunits dissociate, the FRET signal decays to cyan. Although the concept has been tested using only a bacterium, Janetopoulos says that they are developing the technique for mammalian cells. “I think that the technique could and will be used with other receptor systems.”