TY - JOUR T1 - A Perspective on Studying GPCR Signaling with RET Biosensors in Living Organisms JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.115.098897 SP - mol.115.098897 AU - Jakobus van Unen AU - Jeanette Woolard AU - Ago Rinken AU - Carsten Hoffmann AU - Steve Hill AU - Joachim Goedhart AU - Michael Bruchas AU - Michel Bouvier AU - Merel Adjobo-Hermans Y1 - 2015/01/01 UR - http://molpharm.aspetjournals.org/content/early/2015/05/13/mol.115.098897.abstract N2 - The last frontier for a complete understanding of G-protein-coupled receptor (GPCR) biology is to be able to assess GPCR activity, interactions, and signaling in vivo, in real time within biologically intact systems. This includes the ability to detect GPCR trafficking, dimerization, protein-protein interactions and receptor activity dynamically, with high spatial resolution and fast kinetic readouts. Resonance energy transfer (RET)-based biosensors allow for all of these possibilities in vitro, however, moving RET into intact animals has proven difficult. Here, we provide perspectives on the optimization of biosensor design, of signal detection in living organisms as well as the multidisciplinary development of in vitro assays that are more appropriate representatives of the physiological situation. In short, further development of RET-based probes, optical microscopy techniques and mouse genome editing hold great potential over the next decade to bring in vivo real-time GPCR imaging to the forefront of pharmacology. ER -