title: Loss of gq/11 genes does not abolish melanopsin phototransduction.
abstract: 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 Gq/11 family, which consists of Gna11, Gna14, Gnaq and Gna15, in melanopsin-evoked depolarization. However, the exact identity of the Gq/11 gene involved in this process has remained elusive. Additionally, whether Gq/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 Gq/11 family members. All Gq/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 Gq, G11, G14, or G15 alone or in combination are not necessary for melanopsin-based phototransduction, and suggest that ipRGCs may be able to utilize a Gq/11-independent phototransduction cascade in vivo.
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Kylie S
authors.initials: KS
authors.lastname: Chew
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Schmidt
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Rupp
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Paulo
authors.initials: P
authors.lastname: Kofuji
authors.affiliation: Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa, United States of America.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trimarchi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D055537:Light Signal Transduction / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D012025:Reflex, Pupillary / Q000235:genetics* / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017299:Rod Opsins / Q000378:metabolism*; D000099210:Melanopsin
chemical_list: D017931:DNA Primers; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D017299:Rod Opsins; D000099210:Melanopsin; C532882:Galpha14 protein, mouse