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June 7, 2023 • ✎ STRIA TECH

A visual opsin from jellyfish enables precise temporal control of G protein signalling

Topics:

Blindness

Maintaining and Restoring Vision

Optogenetics

Publication

Nature Communications (Apr 28, 2023) A visual opsin from jellyfish enables precise temporal control of G protein signalling

van Wyk M, Kleinlogel S

DOI: 10.1038/s41467-023-38231-z >>

This research focuses on understanding how the rhodopsin protein found in a box jellyfish utilizes a unique Gαs intracellular pathway to achieve fast vision. The study uncovers a mechanism where the rhodopsin protein constitutively binds to a single downstream Gαs partner, enabling rapid activation and inactivation of G-protein signaling within milliseconds. By studying the rhodopsin protein, van Wyk and Kleinlogel engineered an optogenetic tool and used it in viral gene therapy to restore light responses in blind mice.

Phototransduction is mediated by distinct types of G protein cascades in different animal taxa: bilateral invertebrates typically utilise the Gαq pathway whereas vertebrates typically utilise the Gαt(i/o) pathway. By contrast, photoreceptors in jellyfish (Cnidaria) utilise the Gαs intracellular pathway, similar to olfactory transduction in mammals¹. How this habitually slow pathway has adapted to support dynamic vision in jellyfish remains unknown. Here we study a light-sensing protein (rhodopsin) from the box jellyfish Carybdea rastonii and uncover a mechanism that dramatically speeds up phototransduction: an uninterrupted G protein-coupled receptor - G protein complex. Unlike known G protein-coupled receptors (GPCRs), this rhodopsin constitutively binds a single downstream Gαs partner to enable G-protein activation and inactivation within tens of milliseconds. We use this GPCR in a viral gene therapy to restore light responses in blind mice.