Dephosphorylation by protein phosphatase 2A regulates visual pigment regeneration and the dark adaptation of mammalian photoreceptors.
Resetting of G-protein-coupled receptors (GPCRs) from their active state back to their biologically inert ground state is an integral part of GPCR signaling. This "on-off" GPCR cycle is regulated by reversible phosphorylation. Retinal rod and cone photoreceptors arguably represent the best-understood example of such GPCR signaling. Their visual pigments (opsins) are activated by light, transduce the signal, and are then inactivated by a GPCR kinase and arrestin. Although pigment inactivation by phosphorylation is well understood, the enzyme(s) responsible for pigment dephosphorylation and the functional significance of this reaction remain unknown. Here, we show that protein phosphatase 2A (PP2A) acts as opsin phosphatase in both rods and cones. Elimination of PP2A substantially slows pigment dephosphorylation, visual chromophore recycling, and ultimately photoreceptor dark adaptation. These findings demonstrate that visual pigment dephosphorylation regulates the dark adaptation of photoreceptors and provide insights into the role of this reaction in GPCR signaling.
['Kolesnikov|Alexander V|AV|0000-0001-7768-4189', 'Orban|Tivadar|T|', 'Jin|Hui|H|', 'Brooks|Celine|C|', 'Hofmann|Lukas|L|', 'Dong|Zhiqian|Z|', 'Sokolov|Maxim|M|', 'Palczewski|Krzysztof|K|0000-0002-0788-545X', 'Kefalov|Vladimir J|VJ|']
D000818:Animals D019393:Arrestin D003623:Dark Adaptation D005260:Female D008027:Light D008297:Male D008322:Mammals D051379:Mice D055355:Opsins D010766:Phosphorylation D054648:Protein Phosphatase 2 D012038:Regeneration D012160:Retina D017949:Retinal Cone Photoreceptor Cells D055213:Retinal Pigment Epithelium D017948:Retinal Rod Photoreceptor Cells D012243:Rhodopsin
dark adaptation photoreceptors GPCRs PP2A visual cycle