Engineering receptors activated solely by synthetic ligands (RASSLs)

The functional and molecular diversity of G-protein-coupled receptors prese nts a significant challenge to understanding the connection between a singl e receptor signaling pathway and a specific physiological or pathological r esponse. To gain control over the timing and specificity of a G-protein sig nal, receptors activated solely by synthetic ligands (RASSLs) have been dev eloped. These engineered receptors no longer respond to endogenous peptides , but can still be activated by a specific small-molecule drug. Further con trol over the location of the signal can be achieved by using RASSLs in con junction with tissue-specific expression systems in vivo. Existing RASSLs h ave clarified the role of G(i) signaling in cardiac physiology and are curr ently being used to study cardiomyopathy, muscle remodeling, sensory transd uction and complex neurobehavioral responses.