A perfect couple: A visual opsin from the box jellyfish binds Gαs to form a stable protein complex with unparalleled temporal control of Gβγ signalling

Abstract Phototransduction is mediated by distinct types of G-protein cascades in different animal taxa: bilateral invertebrates typically utilize the Gαq pathway whereas vertebrates typically utilize the Gαt(i/o) pathway. By contrast, photoreceptors in jellyfish (Cnidaria) utilize 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 novel mechanism that dramatically speeds up phototransduction. Unlike other 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. This is the first time an uninterrupted G-protein coupled receptor/G-protein complex is described. We use this unique GPCR in a viral gene therapy to restore light responses in blind mice using the previously unforeseen Gαs signalling pathway.