Evolution of Mammalian Opn5 as a Specialized UV-absorbing Pigment by a Single Amino Acid Mutation

Abstract

Background: Opn5 is considered to regulate nonvisual photoreception in the retina and brain of animals. Results: Mouse and primate UV-sensitive Opn5 along with retinoid isomerase are localized in the preoptic hypothalamus. Conclusion: Mammalian Opn5 can function as a high sensitivity photosensor in the deep brain with the assistance of 11-cisretinal supplying system. Significance: Mammals, including humans, may detect short wavelength light within the brain via Opn5.

Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea

“…The concordance between the wavelength dependence of the retinal entrainment and the absorption spectrum of OPN5 (13,16) lends further support to the notion that OPN5 functions as a photopigment for these clocks. As such, we have identified a function for mammalian OPN5, previously an orphan opsin.…”

“…For corneal OPN5, interphotoreceptor retinoid-binding protein in the aqueous and vitreous humors (42) could potentially transport cis-retinal via diffusion from the retina. Because OPN5 appears to be bistable (13,16), similar to bistable/tristable OPN4 (43)(44)(45), this property may explain its sustained photosensitivity under extended culture conditions ex vivo.…”

“…Mouse cornea and lens, unlike their human counterparts, transmit UV-A (40), a property exploited by the abundant blue-cone pigment, OPN1SW, in the mouse retina, and presumably also by OPN5. Even in humans, there is likely enough transmitted blue light in full sunlight for OPN5 to signal, because OPN5's sensitivity at the human blue cone pigment's λ max of 430 nm is only one log-unit lower than at its own λ max of 380 nm [based on heterologous expression (13,16)]. The cis-retinal required by OPN5 as a chromophore (13, 16) could potentially be accessed in the inner retina in the same way as by ipRGCs, possibly from the Müller glial cells (41).…”

“…Mouse OPN5 has a λ max in the UV-A region (380 nm) when heterologously expressed (13,16). For OPN3, heterologously expressed fish and insect homologs have a λ max of 460 nm and 500 nm, respectively (14), but the λ max of mammalian OPN3 is still unknown.…”

“…Because some cone nuclei may persist in degenerate rd1/rd1 retinas (9), and murine short-wavelength-sensitive cone opsin (OPN1SW) has been reported to be present in the ganglion cell layer (10), we tested the necessity of this pigment for local retinal circadian photoentrainment. We also tested for the involvement of two orphan pigments, encephalopsin (OPN3) (11) and neuropsin (OPN5) (12), both of which are expressed in mammalian retina and, when expressed heterologously, form light-sensitive pigments that activate G proteins (13)(14)(15)(16)(17). The function of OPN3 in mammals is unknown despite its widespread expression in neural tissues (18).…”