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C-terminal phosphorylation regulates the kinetics of a subset of melanopsin-mediated behaviors in mice.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Mar 07; Vol. 114 (10), pp. 2741-2746. Date of Electronic Publication: 2017 Feb 21. - Publication Year :
- 2017
-
Abstract
- Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and mediate several non-image-forming visual functions, including circadian photoentrainment and the pupillary light reflex (PLR). ipRGCs act as autonomous photoreceptors via the intrinsic melanopsin-based phototransduction pathway and as a relay for rod/cone input via synaptically driven responses. Under low light intensities, where only synaptically driven rod/cone input activates ipRGCs, the duration of the ipRGC response will be determined by the termination kinetics of the rod/cone circuits. Little is known, however, about the termination kinetics of the intrinsic melanopsin-based phototransduction pathway and its contribution to several melanopsin-mediated behaviors. Here, we show that C-terminal phosphorylation of melanopsin determines the recovery kinetics of the intrinsic melanopsin-based photoresponse in ipRGCs, the duration of the PLR, and the speed of reentrainment. In contrast, circadian phase alignment and direct effects of light on activity (masking) are not influenced by C-terminal phosphorylation of melanopsin. Electrophysiological measurements demonstrate that expression of a virally encoded melanopsin lacking all C-terminal phosphorylation sites (C terminus phosphonull) leads to a prolonged intrinsic light response. In addition, mice expressing the C terminus phosphonull in ipRGCs reentrain faster to a delayed light/dark cycle compared with mice expressing virally encoded WT melanopsin; however, the phase angle of entrainment and masking were indistinguishable. Importantly, a sustained PLR in the phosphonull animals is only observed at brighter light intensities that activate melanopsin phototransduction, but not at dimmer light intensities that activate only the rod/cone pathway. Taken together, our results highlight how the kinetics of the melanopsin photoresponse differentially regulate distinct light-mediated behaviors.
- Subjects :
- Animals
Circadian Rhythm genetics
Kinetics
Light
Light Signal Transduction physiology
Mice
Patch-Clamp Techniques
Phosphorylation genetics
Photoreceptor Cells, Vertebrate metabolism
Photoreceptor Cells, Vertebrate physiology
Reflex, Pupillary genetics
Reflex, Pupillary physiology
Retina metabolism
Retina physiology
Retinal Ganglion Cells physiology
Rod Opsins chemistry
Rod Opsins genetics
Synapses genetics
Synapses metabolism
Vision, Ocular genetics
Vision, Ocular physiology
Behavior, Animal
Light Signal Transduction genetics
Retinal Ganglion Cells metabolism
Rod Opsins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 114
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 28223508
- Full Text :
- https://doi.org/10.1073/pnas.1611893114