Single-chain fluorescent integrators for mapping G-protein-coupled receptor agonists
Kayla Kroning1,2, Noam Gannot1,3, Xingyu Li1,3,4
1Life Sciences Institute, University of Michigan, Ann Arbor, MI.
Biorxiv : the Preprint Server for Biology
|July 3, 2023
Summary
New SPOTall sensors detect G protein-coupled receptor (GPCR) agonist localization in the whole brain. This platform enables unbiased detection of neuromodulators, advancing neuroscience research.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- G protein-coupled receptors (GPCRs) mediate the effects of crucial neuromodulators like dopamine, serotonin, and opioids.
- Understanding the precise localization of GPCR agonists is vital for deciphering their impact on neuronal pathways.
Approach:
- Developed a novel sensor design platform, SPOTall, for engineering GPCR agonist integrator sensors.
- Engineered sensors for beta-2-adrenergic receptor (B2AR), dopamine D1, and muscarinic 2 receptor agonists.
- Created a red fluorescent variant of existing SPOTIT sensors for multiplexed imaging.
Key Points:
- Successfully engineered SPOTall sensors for B2AR and dopamine D1 receptors.
- Demonstrated the detection of morphine, isoproterenol, and epinephrine in mouse brains using M-SPOTIT and B2AR-SPOTall sensors.
- The SPOTIT and SPOTall platforms facilitate the design of diverse GPCR sensors.
Conclusions:
- The SPOTall platform offers a versatile tool for creating GPCR integrator sensors.
- This technology enables unbiased, whole-brain detection of various synthetic and endogenous neuromodulators.
- Advances the study of neuromodulation and drug action in the brain.
Related Concept Videos
01:21G-protein Coupled Receptors
120.3K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
120.3K
01:15G Protein-coupled Receptors
12.3K
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.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
12.3K