Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors

The mammalian retina harbors a circadian clockwork that regulates vision and promotes healthiness of retinal neurons, mainly through directing the rhythmic release of the neurohormones dopamine—acting on dopamine D(4) receptors—and melatonin—acting on MT(1) and MT(2) receptors. The gene Gnaz—a unique Gi/o subfamily member—was seen in the present study to be expressed in photoreceptors where its protein product Gα(z) shows a daily rhythm in its subcellular localization. Apart from subcellular localization, Gnaz displays a daily rhythm in expression—with peak values at night—in preparations of the whole retina, microdissected photoreceptors and photoreceptor-related pinealocytes. In retina, Gnaz rhythmicity was observed to persist under constant darkness and to be abolished in retina deficient for Clock or dopamine D(4) receptors. Furthermore, circadian regulation of Gnaz was disturbed in the db/db mouse, a model of diabetic retinopathy. The data of the present study suggest that Gnaz links the circadian clockwork—via dopamine acting on D(4) receptors—to G protein-mediated signaling in intact but not diabetic retina.