title: Cellular and subcellular context determine outputs from signaling biosensors.
abstract: The use of biosensors either individually or as part of panels has now become a common technique to capturing signaling events in living cells. Such biosensors have become particularly important for probing biased signaling and allostery in G protein-coupled receptor drug screening efforts. However, assumptions about the portability of such biosensors between cell types may lead to misinterpretation of drug effects on specific signaling pathways in a given cellular context. Further, the output of a particular biosensor may be different depending on where it is localized in a cell. Here, we discuss strategies to mitigate these concerns which should feed into future biosensor design and usage.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada.
authors.forename: Dominic
authors.initials: D
authors.lastname: Devost
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Audet
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Bonin
authors.affiliation: Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada.
authors.forename: Viktorya
authors.initials: V
authors.lastname: Lukashova
authors.affiliation: Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Le Gouill
authors.affiliation: Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Bouvier
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada.
authors.forename: Terence E
authors.initials: TE
authors.lastname: Hébert
mesh_terms: D015374:Biosensing Techniques; D002467:Cell Nucleus / Q000201:enzymology; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D043562:Receptors, G-Protein-Coupled; D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate
keywords: Biosensors; G protein-coupled receptors; GPCRs; Resonance energy transfer; Signal profiling; Signaling