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 neuro-hormones dopamine-acting on dopamine D-4 receptors-and melatonin-acting on MT1 and MT2 receptors. The gene Gnaz D a unique Gi/o subfamily member D was seen in the present study to be expressed in photoreceptors where its protein product G alpha(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 D to G protein-mediated signaling in intact but not diabetic retina.