Loss of G(q/11) Genes Does Not Abolish Melanopsin Phototransduction

In mammals, a subset of retinal ganglion cells (RGCs) expresses the photopigment melanopsin, which renders them intrinsically photosensitive (ipRGCs). These ipRGCs mediate various non-image-forming visual functions such as circadian photoentrainment and the pupillary light reflex (PLR). Melanopsin phototransduction begins with activation of a heterotrimeric G protein of unknown identity. Several studies of melanopsin phototransduction have implicated a G-protein of the G(q/11) family, which consists of Gna11, Gna14, Gnaq and Gna15, in melanopsin-evoked depolarization. However, the exact identity of the G(q/11) gene involved in this process has remained elusive. Additionally, whether G(q/11) G-proteins are necessary for melanopsin phototransduction in vivo has not yet been examined. We show here that the majority of ipRGCs express both Gna11 and Gna14, but neither Gnaq nor Gna15. Animals lacking the melanopsin protein have well-characterized deficits in the PLR and circadian behaviors, and we therefore examined these non-imaging forming visual functions in a variety of single and double mutants for G(q/11) family members. All G(q/11) mutant animals exhibited PLR and circadian behaviors indistinguishable from WT. In addition, we show persistence of ipRGC light-evoked responses in Gna11(−/−); Gna14(−/−) retinas using multielectrode array recordings. These results demonstrate that G(q), G(11), G(14), or G(15) alone or in combination are not necessary for melanopsin-based phototransduction, and suggest that ipRGCs may be able to utilize a G(q/11)-independent phototransduction cascade in vivo.