PT  - JOURNAL ARTICLE
AU  - Jakobus van Unen
AU  - Jeanette Woolard
AU  - Ago Rinken
AU  - Carsten Hoffmann
AU  - Stephen J. Hill
AU  - Joachim Goedhart
AU  - Michael R. Bruchas
AU  - Michel Bouvier
AU  - Merel J. W. Adjobo-Hermans
TI  - A Perspective on Studying G-Protein–Coupled Receptor Signaling with Resonance Energy Transfer Biosensors in Living Organisms
AID  - 10.1124/mol.115.098897
DP  - 2015 Sep 01
TA  - Molecular Pharmacology
PG  - 589--595
VI  - 88
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/88/3/589.short
4100  - http://molpharm.aspetjournals.org/content/88/3/589.full
SO  - Mol Pharmacol2015 Sep 01; 88
AB  - 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 activity, trafficking, dimerization, protein-protein interactions, second messenger production, and downstream signaling events with high spatial resolution and fast kinetic readouts. Resonance energy transfer (RET)–based biosensors allow for all of these possibilities in vitro and in cell-based assays, but moving RET into intact animals has proven difficult. Here, we provide perspectives on the optimization of biosensor design, of signal detection in living organisms, and the multidisciplinary development of in vitro and cell-based assays that more appropriately reflect the physiologic 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 real-time in vivo GPCR imaging to the forefront of pharmacology.