title: G-Protein Coupled Receptor Kinase 2 Minimally Regulates Melanopsin Activity in Intrinsically Photosensitive Retinal Ganglion Cells.
abstract: Phosphorylation is a primary modulator of mammalian G-protein coupled receptor (GPCR) activity. The GPCR melanopsin is the photopigment of intrinsically photosensitive retinal ganglion cells (ipRGCs) in the mammalian retina. Recent evidence from in vitro experiments suggests that the G-protein coupled receptor kinase 2 (GRK2) phosphorylates melanopsin and reduces its activity following light exposure. Using an ipRGC-specific GRK2 loss-of-function mouse, we show that GRK2 loss alters melanopsin response dynamics and termination time in postnatal day 8 (P8) ipRGCs but not in older animals. However, the alterations are small in comparison to the changes reported for other opsins with loss of their cognate GRK. These results suggest GRK2 contributes to melanopsin deactivation, but that other mechanisms account for most of modulation of melanopsin activity in ipRGCs.
authors.affiliation: Department of Ophthalmology, University of Washington School of Medicine, Seattle, Washington, United States of America; Program in Neurobiology and Behavior, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Sexton
authors.affiliation: Department of Ophthalmology, University of Washington School of Medicine, Seattle, Washington, United States of America; Department of Pathology, University of Washington School of Medicine, Seattle, Washington, United States of America; Department of Biological Structure, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Russell N
authors.initials: RN
authors.lastname: Van Gelder
mesh_terms: D000818:Animals; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D000099210:Melanopsin
chemical_list: D054769:G-Protein-Coupled Receptor Kinase 2; D017299:Rod Opsins; D000099210:Melanopsin; C496568:GRK2 protein, mouse