TY - JOUR
T1 - C-terminal phosphorylation regulates the kinetics of a subset of melanopsin-mediated behaviors in mice
AU - Somasundaram, Preethi
AU - Wyrick, Glenn R.
AU - Fernandez, Diego Carlos
AU - Ghahari, Alireza
AU - Pinhal, Cindy M.
AU - Richardson, Melissa Simmonds
AU - Rupp, Alan C.
AU - Cui, Lihong
AU - Wu, Zhijian
AU - Brown, R. Lane
AU - Badea, Tudor Constantin
AU - Hattar, Samer
AU - Robinson, Phyllis R.
N1 - Publisher Copyright:
© 2017, National Academy of Sciences. All rights reserved.
PY - 2017/3/7
Y1 - 2017/3/7
N2 - 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 high-light how the kinetics of the melanopsin photoresponse differentially regulate distinct light-mediated behaviors.
AB - 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 high-light how the kinetics of the melanopsin photoresponse differentially regulate distinct light-mediated behaviors.
KW - Phosphorylation
KW - Photoentrainment
KW - Photoreceptors
KW - Phototransduction
KW - ipRGCs
UR - http://www.scopus.com/inward/record.url?scp=85014724145&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014724145&partnerID=8YFLogxK
U2 - 10.1073/pnas.1611893114
DO - 10.1073/pnas.1611893114
M3 - Article
C2 - 28223508
AN - SCOPUS:85014724145
SN - 0027-8424
VL - 114
SP - 2741
EP - 2746
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 10
ER -