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Takesi Matsuyama, Yoshinori Shichida, Masayo Takahashi; Melanopsin tristability for robust and sustained photoreception under various light conditions. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1981.
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© ARVO (1962-2015); The Authors (2016-present)
Melanopsin, the photosensitive pigment of ipRGCs, is phylogenetically closely related to invertebrate visual pigments, which are characterized by a photo-labile reaction (bistability). Previously, we showed that melanopsin has a second photo-labile state and therefore is tristable rather than bistable. However, very few studies so far have accounted for this property and it is very often assumed that melanopsin action spectrum can be approximated to 480nm single peak opsin template. Here we investigated photochemical and biochemical properties of this new tristable photoreaction, and explore how it could impact melanopsin mediated photo responses and how it can be reconciled with reported melanopsin action spectrum.
Melanopsin photochemical properties were investigated by UV/Vis spectroscopy of exogenously expressed and purified melanopsin extracts. G-protein activation characterization was carried out by the TGFalpha-AP Gq activation assay on melanopsin expressing HEK293 cells.
We estimated all of the kinetic parameters characterizing melanopsin tristability and characterized the Gq activity of each of the states. Based on these parameters we can predict the activity of melanopsin under different light conditions. Our tristable model indicates that different states of melanopsin can form preferentially, depending on the wavelength of light stimulation. Furthermore, we show that action spectrum of melanopsin is dependent on the intensity and/or duration of the light stimuli, adding another dimension to the photoresponse of melanopsin. Simulation of action spectrum derived from the tristable model shows that tristability is consistent with published reports. Furthermore, our new modol seems to acount for some inconsistencies in previous reports.
We have conducted a comprehensive analysis of melanopsin photochemistry and its G-protein activity, and build a model of melanopsin photoresponse. Together our results show that melanopsin is capable of mediating a robust response under different light conditions. Our model shows that at lower light intensities melanopsin reaction can be reasonably approximated with a single peak opsin template, but the behavior at higher light intensities where photo-steady state dynamic comes into play can be more complex than previously thought.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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