Table 1.

Resonance energy transfer biosensors for GPCR activation

GPCR	Resonance technique	Comments	Reference
Receptor subtype
PTH receptor sensor and α2A‐adrenoceptor sensor with CFP/YFP	FRET	First sensor for GPCR activation based on FRET which was designed to study conformational changes in living cells	Vilardaga et al. 2003
mGlu1 receptor CFP/YFP	FRET	Inter‐subunit FRET change between protomers, but no intra‐subunit FRET change	Tateyama et al. 2004
A2A receptor sensor with FlAsH/CFP or CFP/YFP	FRET	First sensor using the combination FlAsH/CFP which showed no disturbance of G‐protein signalling	Hoffmann et al. 2005
α2A adrenoceptor sensor with constitutive activity CFP/YFP	FRET	Inverse agonists exhibit signals opposite to that of agonists	Vilardaga et al. 2005
B2 receptor sensor CFP/YFP	FRET	B2‐bradykinin receptor sensor responded to mechanosensitive stimuli	Chachisvilis et al., 2006
α2A‐adrenoceptor sensor FlAsH/CFP	FRET	Partial and full agonists exhibit distinct receptor activation kinetics	Nikolaev et al. 2006
β2‐adrenoceptor FlAsH/CFP	FRET	First sensor to observe an increase in FRET ratio upon agonist stimulation	Nakanishi et al. 2006
β1‐adrenoceptor CFP/YFP	FRET	Clinically used antagonists exhibit different FRET signals for different polymorphic receptor variants	Rochais et al. 2007
α2A‐adrenoceptor sensor FlAsH/CFP	FRET	Receptor crosstalk between α2A‐adrenergic receptor and μ‐opioid receptor shown by influence of the FRET signal	Vilardaga et al. 2008
α2A‐adrenoceptor sensor FlAsH/CFP	FRET	Labelling with FlAsH in different positions reveals that partial agonists only induce conformational changes in some parts of the third intracellular loop	Zürn et al. 2009
M1 receptor CFP/YFP	FRET	Complete kinetic analysis of the signalling cascade of the M1‐ACh‐receptor down to PLC	Jensen et al. 2009
M2 receptor FlAsH/CFP	FRET	Allosteric modulation shown by alterations in the measured FRET signal	Maier‐Peuschel et al. 2010
β2‐adrenoceptor CFP/YFP	FRET	Distinct conformational changes of adrenaline and noradrenaline	Reiner et al. 2010
A2A receptor sensor with FlAsH/ReAsH	FRET	First receptor sensor that did not utilize a fluorescent protein, FRET efficiency determined by acceptor photobleaching	Zürn et al. 2010
GABAB receptor Cerulean/YFP and M1 receptor Cerulean/YFP	FRET	Inter‐subunit FRET change between protomers, but no intra‐subunit FRET change; M1 receptor served as control	Matsushita et al. 2010
M1, M3 and M5 receptor FlAsH/CFP	FRET	Comparison of different muscarinic receptor subtypes reveals differences in ligand‐dependent receptor kinetics	Ziegler et al. 2011
B1 receptor FlAsH/CFP	FRET	Bradykinin‐dependent receptor activation is influenced by heterodimerization with carboxypeptidase M	Zhang et al. 2011
M3 receptor FlAsH/CFP	FRET	M3 receptor and RASSL variant of M3 receptor exhibit similar conformational changes	Alvarez‐Curto et al. 2011
β2‐adrenoceptor CFP/YFP	FRET	Receptor activation kinetics can be influenced by polymorphism	Ahles et al. 2011
5‐HT1B receptor Cerulean/Citrine	FRET	5‐HT1B receptor sensor responded to mechanosensitive stimuli	Candelario and Chachisvilis, 2012
AT1 receptor YFP/RLuc	BRET	First intra‐molecular GPCR based BRET sensor, allosteric modulation of protomers within a receptor dimer	Szalai et al. 2012
M1 receptor CFP/YFP	FRET	Comparison of orthosteric and allosteric ligands	Markovic et al. 2012
V2 receptor FlAsH/Lumi‐4 Tb	LRET	Structural information about biased agonism	Rahmeh et al. 2012
mGlu1 receptor CFP/YFP	FRET	Inter‐subunit FRET change between protomers proceeds intra‐subunit FRET change	Hlavackova et al., 2012
α2A‐adrenoceptor sensor with FlAsH/CFP	FRET	Non‐equilibrium activation demonstrates that G‐protein signalling and signal amplification are highly time‐dependent phenomena	Ambrosio and Lohse, 2012
OX1 and OX2 receptors FlAsH/CFP	FRET	Slow activation kinetics observed as seen for the PTH receptor	Xu et al. 2012
M3 receptor with constitutive activity FlAsH/CFP	FRET	Constitutive receptor activity increases affinity for ACh solely by increase in ligand off‐rate	Hoffmann et al. 2012
M1 receptor FlAsH/CFP	FRET	Improved sensor performance by use of circular permutated versions of CFP	Chang and Ross, 2012
M2 receptor FlAsH/CFP	FRET	Dualsteric receptor ligands exhibit distinct receptor conformations	Bock et al. 2012
B1 receptor FlAsH/CFP and FlAsH/RLuc	FRET/BRET	Carboxypeptidase M influences bradykinin‐dependent receptor activation by allosteric mechanism	Zhang et al. 2013
α2A‐adrenoceptor sensor with CFP/YFP	FRET	Receptor function is regulated by voltage	Rinne et al. 2013
β1‐adrenoceptor CFP/YFP	FRET	Receptor sensor was used to monitor conformational changes evoked by human autoantibodies against β1‐AR in patients suffering from dilated cardiomyopathy	Bornholz et al. 2013
M1 receptor CFP/YFP	FRET	Interaction of receptor and Gq‐protein stabilizes the active receptor state and delays receptor deactivation	Tateyama and Kubo, 2013b
M3 receptor and P2Y1 receptor CFP/YFP	FRET	Differentially influence of Gq‐protein on the active receptor state reveals receptor‐specific influence	Tateyama and Kubo, 2013a
M2 receptor FlAsH/CFP	FRET	Binding pose of dualsteric receptor ligands can dictate partial agonism	Bock et al. 2014
A2A receptor sensor with FlAsH/CFP	FRET	Caffeine described as inverse agonist	Fernandez‐Duenas et al. 2014
β1‐adrenoceptor CFP/YFP	FRET	Receptor polymorphism exhibits different receptor kinetics caused by receptor phosphorylation	Ahles et al. 2015
Ghrelin receptor	LRET	First sensor using unnatural amino acid labelling incorporated by AMBER codon technology, purified receptors in lipid disks	Damian et al. 2015

This table summarizes all articles that we found performing a search for such biosensors listed in PubMed using the search GPCR and FRET (127 hits as of 1 September 2015), GPCR and BRET (106 hits as of 1 September 2015), GPCR and conformational sensor (9 hits as of 1 September 2015) as well as citations listed in Thomson Reuter science citation index to Vilardaga et al. 2003 or Hoffmann et al. 2005. LRET, luminescence resonance energy transfer.