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Abstract
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.
Footnotes
- Received March 10, 2015.
- Accepted May 13, 2015.
This work was supported by the National Institutes of Health National Institute on Drug Abuse [R01-DA033396] (to M.R.B.) and by the Estonian Ministry of Education and Research [IUT20-17] (to A.R.).
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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