Photoswitchable optoGPCRs for reversible control of Gs signalling and arrestin recruitment

bioRxiv · 12 Nov 2026 · Preprint · Open access

Walter, McDowell + 6 more

The abstract is read at the publisher; the summary is JClub's.

OptoDRD1, a bistable JSR1-S199F-based optoGPCR, enables reversible violet/green light control of Gs signalling with sustained cAMP output and rapid deactivation.

Why it matters: Existing optoGPCRs are often monostable, limiting experiments by photobleaching and irreversibility, and leaving few reversible tools for Gs pathways.
What they did: The authors engineered JSR1-S199F using AlphaFold-guided receptor–miniGs design and screened intracellular domain chimeras, identifying ICL2, ICL3, helix 8, and the DRD1 C-terminus; optoDRD1 uses {lambda}max 397 nm and 531 nm.
The result: A single violet pulse sustains Gs signalling for several hours, while green light deactivates at chosen time points over multiple cycles, matching wild-type DRD1 cAMP kinetics and enabling optogenetic control of insulin secretion in human beta-cells and neuronal signalling.

AI summary of the abstract · may contain errors · not medical advice · read the paper.

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Photoswitchable optoGPCRs for reversible control of Gs signalling and arrestin recruitment

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