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A light-responsive fungal guanylyl cyclase provides a tool with which to study cGMP signaling in mammalian systems. Lighting up cGMP signaling The second messenger cyclic guanosine monophosphate (cGMP) alters ion channel activity to mediate processes such as smooth muscle relaxation, transduction of light, and apoptosis. Guanylyl cyclases produce cGMP from GTP. Scheib et al. characterized the fungal photoreceptor RhGC, which consists of the light-sensitive receptor rhodopsin connected to a guanylyl cyclase. When expressed in mammalian cells, including neurons, light stimulated RhGC to generate cGMP. Thus, RhGC is another tool in the optogenetic kit and can be used to study cGMP signaling. Blastocladiomycota fungi form motile zoospores that are guided by sensory photoreceptors to areas of optimal light conditions. We showed that the microbial rhodopsin of Blastocladiella emersonii is a rhodopsin–guanylyl cyclase (RhGC), a member of a previously uncharacterized rhodopsin class of light-activated enzymes that generate the second messenger cyclic guanosine monophosphate (cGMP). Upon application of a short light flash, recombinant RhGC converted within 8 ms into a signaling state with blue-shifted absorption from which the dark state recovered within 100 ms. When expressed in Xenopus oocytes, Chinese hamster ovary cells, or mammalian neurons, RhGC generated cGMP in response to green light in a light dose–dependent manner on a subsecond time scale. Thus, we propose RhGC as a versatile tool for the optogenetic analysis of cGMP-dependent signaling processes in cell biology and the neurosciences.

The rhodopsin–guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling