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Updated: Sep 30, 2025

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
Divergent G-protein selectivity across melanopsins from mice and humans
Richard J McDowell1, Jessica Rodgers1, Nina Milosavljevic1
1Centre for Biological Timing, Division of Neuroscience and Experimental Psychology, Faculty of Biology Medicine and Health, University of Manchester, Manchester M13 9PT, UK.
Abstract:
Melanopsin is an opsin photopigment and light-activated G-protein-coupled receptor; it is expressed in photoreceptive retinal ganglion cells (mRGCs) and can be employed as an optogenetic tool. Mammalian melanopsins can signal via Gq/11 and Gi/o/t heterotrimeric G proteins, but aspects of the mRGC light response appear incompatible with either mode of signalling. We use live-cell reporter assays in HEK293T cells to show that melanopsins from mice and humans can also signal via Gs. We subsequently show that this mode of signalling is substantially divergent between species. The two established structural isoforms of mouse melanopsin (which differ in the length of their C-terminal tail) both signalled strongly through all three G-protein classes (Gq/11, Gi/o and Gs), whereas human melanopsin showed weaker signalling through Gs. Our data identify Gs as a new mode of signalling for mammalian melanopsins and reveal diversity in G-protein selectivity across mammalian melanopsins.
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