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Updated: Jun 9, 2026

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G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
Published on: September 10, 2016
SENSIT, a Modular Single-Chain Fluorescent Integrator Platform for GPCR Ligands.
Aubrey Putansu1,2, Isabel Solowiej1,2, Hannah Rivett-Trznadel1,2
1Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
ACS Chemical Biology
|June 8, 2026
Summary
Researchers developed a new tool, the single-chain expressing neurotransmitter sensing integrator tool (SENSIT), to map neurotransmitter release in the brain. This platform enables high-resolution whole-brain mapping of specific neurotransmitters like epinephrine and norepinephrine.
Area of Science:
- Neuroscience
- Molecular Biology
- Biotechnology
Background:
- G-protein-coupled receptors (GPCRs) are crucial for neurotransmission but visualizing their activity across large brain volumes at high resolution is challenging.
- Existing methods struggle to provide detailed insights into neurotransmitter release dynamics and localization.
Purpose of the Study:
- To develop a novel modular platform for high-resolution neurotransmitter sensing across large brain volumes.
- To create specific reporters for catecholamines and acetylcholine using the developed platform.
- To enable generalized sensor design for diverse neurotransmitters for potential whole-brain mapping.
Main Methods:
- Designed a modular platform named single-chain expressing neurotransmitter sensing integrator tool (SENSIT) utilizing bifunctional chimeric nanobodies.
- Applied SENSIT to create reporters for epinephrine and norepinephrine with high selectivity.
- Developed a muscarinic acetylcholine receptor 2 (CHRM2)-based sensor and chimeric miniG proteins to demonstrate platform modularity.
Main Results:
- Epinephrine and norepinephrine reporters demonstrated 20-fold and 5-fold selectivity, respectively, over other catecholamines.
- Successfully developed a CHRM2-based sensor, showcasing the platform's versatility.
- The SENSIT platform represents the first single-chain integrator sensor capable of distinguishing between epinephrine and norepinephrine.
Conclusions:
- The SENSIT platform offers a powerful, modular approach for high-resolution neurotransmitter sensing.
- This technology enables the distinction of specific catecholamines and has potential for broad application in neuroscience research.
- SENSIT paves the way for generalized integrator sensor design and whole-brain mapping of neurotransmitter activity.
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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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