Proceedings of the National Academy of Sciences - PNAS, 2024-04, Vol.121 (18), p.e2307090121
2024
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- Autor(en) / Beteiligte
- Titel
- Single-chain fluorescent integrators for mapping G-protein-coupled receptor agonists
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2024-04, Vol.121 (18), p.e2307090121
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2024
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- G protein-coupled receptors (GPCRs) transduce the effects of many neuromodulators including dopamine, serotonin, epinephrine, acetylcholine, and opioids. The localization of synthetic or endogenous GPCR agonists impacts their action on specific neuronal pathways. In this paper, we show a series of single-protein chain integrator sensors that are highly modular and could potentially be used to determine GPCR agonist localization across the brain. We previously engineered integrator sensors for the mu- and kappa-opioid receptor agonists called M- and K-Single-chain Protein-based Opioid Transmission Indicator Tool (SPOTIT), respectively. Here, we engineered red versions of the SPOTIT sensors for multiplexed imaging of GPCR agonists. We also modified SPOTIT to create an integrator sensor design platform called SPOTIT for all GPCRs (SPOTall). We used the SPOTall platform to engineer sensors for the beta 2-adrenergic receptor (B2AR), the dopamine receptor D1, and the cholinergic receptor muscarinic 2 agonists. Finally, we demonstrated the application of M-SPOTIT and B2AR-SPOTall in detecting exogenously administered morphine, isoproterenol, and epinephrine in the mouse brain via locally injected viruses. The SPOTIT and SPOTall sensor design platform has the potential for unbiased agonist detection of many synthetic and endogenous neuromodulators across the brain.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424, 1091-6490eISSN: 1091-6490DOI: 10.1073/pnas.2307090121Titel-ID: cdi_pubmed_primary_38648487
- Format
- –
- Schlagworte
- Acetylcholine receptors, Acetylcholine receptors (muscarinic), Adrenergic receptors, Agonists, Animals, Biological Sciences, Biosensing Techniques - methods, Brain, Brain - diagnostic imaging, Brain - drug effects, Brain - metabolism, Cholinergics, Dopamine, Dopamine D1 receptors, Epinephrine, Fluorescence, G protein-coupled receptors, HEK293 Cells, Humans, Integrators, Isoproterenol - pharmacology, Localization, Mice, Morphine, Morphine - pharmacology, Narcotics, Neuroimaging, Neuromodulation, Neurotransmitters, Opioid receptors (type kappa), Opioid receptors (type mu), Peptide mapping, Proteins, Receptor, Muscarinic M2 - agonists, Receptor, Muscarinic M2 - metabolism, Receptors, Receptors (physiology), Receptors, Adrenergic, beta-2 - genetics, Receptors, Adrenergic, beta-2 - metabolism, Receptors, Dopamine D1 - agonists, Receptors, Dopamine D1 - metabolism, Receptors, G-Protein-Coupled - agonists, Receptors, G-Protein-Coupled - metabolism, Receptors, Opioid, kappa - agonists, Receptors, Opioid, kappa - metabolism, Receptors, Opioid, mu - agonists, Receptors, Opioid, mu - metabolism, Sensors, Serotonin, Viruses