Source 1review2011Pharmacological Reviews
Toolkit/designer GPCRs
designer GPCRs
Also known as: designer receptors exclusively activated by designer drugs, DREADDs, receptors activated solely by synthetic ligands
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
We focus primarily on designer GPCRs (receptors activated solely by synthetic ligands, designer receptors exclusively activated by designer drugs)
Usefulness & Problems
Why this is useful
Designer GPCRs are engineered receptors used for remote control of neuronal signaling by synthetic ligands. In the review abstract they are presented as a primary tool class for activating or inhibiting neuronal firing.; remote manipulation of neuronal signaling; bidirectional control of neuronal firing; probing links between brain activity and behavior
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Designer GPCRs are engineered receptors used for remote control of neuronal signaling by synthetic ligands. In the review abstract they are presented as a primary tool class for activating or inhibiting neuronal firing.
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remote manipulation of neuronal signaling
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bidirectional control of neuronal firing
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probing links between brain activity and behavior
Problem solved
They help neuroscientists manipulate neuronal activity remotely to study how circuit activity relates to behavior.; enables synthetic-ligand control of GPCR signaling in neurons
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They help neuroscientists manipulate neuronal activity remotely to study how circuit activity relates to behavior.
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enables synthetic-ligand control of GPCR signaling in neurons
Problem links
enables synthetic-ligand control of GPCR signaling in neurons
LiteratureThey help neuroscientists manipulate neuronal activity remotely to study how circuit activity relates to behavior.
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They help neuroscientists manipulate neuronal activity remotely to study how circuit activity relates to behavior.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Techniques
Computational DesignTarget processes
signalingInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: regulatorswitch architecture: uncaging
Use of these tools requires the engineered receptor and an orthogonal activating ligand such as a synthetic small molecule or peptide. The abstract only supports this at the level of ligand-based GPCR control.; requires synthetic ligands; acts through GPCR signaling
The abstract states that no tool in this set is perfect and that tradeoffs remain in timing, spatial resolution, and invasiveness.; none of these tools is perfect; tradeoffs exist in kinetics, spatial resolution, and invasiveness
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
The reviewed remote-control tools differ in effect direction, onset and offset kinetics, spatial resolution, and invasiveness.
None of the reviewed neuronal remote-control tools is perfect, and each has advantages and disadvantages.
The reviewed tools use light, peptides, and small molecules to primarily activate ion channels and GPCRs, thereby activating or inhibiting neuronal firing.
Remote bidirectional manipulation of neuronal electrical and chemical signaling with high spatiotemporal precision is presented as an ideal approach for linking neural activity to behavior.
Approval Evidence
1 source4 linked approval claimsfirst-pass slug designer-gpcrs
We focus primarily on designer GPCRs (receptors activated solely by synthetic ligands, designer receptors exclusively activated by designer drugs)
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comparison summarysupports
The reviewed remote-control tools differ in effect direction, onset and offset kinetics, spatial resolution, and invasiveness.
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limitation summarysupports
None of the reviewed neuronal remote-control tools is perfect, and each has advantages and disadvantages.
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mechanism summarysupports
The reviewed tools use light, peptides, and small molecules to primarily activate ion channels and GPCRs, thereby activating or inhibiting neuronal firing.
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review scope summarysupports
Remote bidirectional manipulation of neuronal electrical and chemical signaling with high spatiotemporal precision is presented as an ideal approach for linking neural activity to behavior.
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Comparisons
Source-stated alternatives
The review contrasts designer GPCRs with microbial opsins and also mentions orthogonal receptors, caged ligands, and allosteric modulators as other approaches.
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The review contrasts designer GPCRs with microbial opsins and also mentions orthogonal receptors, caged ligands, and allosteric modulators as other approaches.
Source-backed strengths
supports remote manipulation; part of a toolkit offering varying spatial, temporal, and directional control
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supports remote manipulation
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part of a toolkit offering varying spatial, temporal, and directional control
Compared with opsins
The review contrasts designer GPCRs with microbial opsins and also mentions orthogonal receptors, caged ligands, and allosteric modulators as other approaches.
Shared frame: source-stated alternative in extracted literature
Strengths here: supports remote manipulation; part of a toolkit offering varying spatial, temporal, and directional control.
Relative tradeoffs: none of these tools is perfect; tradeoffs exist in kinetics, spatial resolution, and invasiveness.
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The review contrasts designer GPCRs with microbial opsins and also mentions orthogonal receptors, caged ligands, and allosteric modulators as other approaches.
Ranked Citations
- 1.