Illumination of the Melanopsin Signaling Pathway

Abstract

In mammals, a small population of intrinsically photosensitive retinal ganglion cells (ipRGCs) plays a key role in the regulation of nonvisual photic responses, such as behavioral responses to light, pineal melatonin synthesis, pupillary light reflex, and sleep latency. These ipRGCs also express melanopsin (Opn4), a putative opsin-family photopigment that has been shown to play a role in mediating these nonvisual photic responses. Melanopsin is required for the function of this inner retinal pathway, but its precise role in generating photic responses has not yet been determined. We found that expression of melanopsin in Xenopus oocytes results in light-dependent activation of membrane currents through the Galpha(q)/Galpha(11) G protein pathway, with an action spectrum closely matching that of melanopsin-expressing ipRGCs and of behavioral responses to light in mice lacking rods and cones. When coexpressed with arrestins, melanopsin could use all-trans-retinaldehyde as a chromophore, which suggests that it may function as a bireactive opsin. We also found that melanopsin could activate the cation channel TRPC3, a mammalian homolog of the Drosophila phototransduction channels TRP and TRPL. Melanopsin therefore signals more like an invertebrate opsin than like a classical vertebrate rod-and-cone opsin.

Sea urchin tube feet are photosensory organs that express a rhabdomeric-like opsin and PAX6

“…The rhabdomeric photoreceptor cells may have transformed into ganglion cells expressing melanopsin, acquiring a new role in light detection and signal transduction [49]. First described in Xenopus, melanopsin is now known to confer photosensitivity on non-photosensitive cells types [50,51]. It has been hypothesized that melanopsin sets the circadian clock through non-ocular light detection [52], and is also expressed in sea urchins [30].…”

Phototransduction and retinal degeneration in Drosophila

“…The cascade in the ipRGCs is initiated through a receptor, melanopsin, which has greater sequence and biophysical similarities to the Drosophila rhodopsins [12][13][14][15][16][17][18] than the light receptors in rods and cones. Furthermore, pharmacological and electrophysiological studies suggest that the ipRGC cascade functions through a PLC and opening of channels that display features reminiscent of TRP channels [19][20][21]. Although, most of the specific signaling proteins in the ipRGCs remain to be identified, it appears that the Drosophila and mammalian ipRGC phototransduction cascades share common origins.…”

Inner retinal photoreception independent of the visual retinoid cycle

“…Mice with nonfunctional or degenerated rods and cones that also lack melanopsin show no photically influenced behavior or physiology (9,10), and intrinsic photosensitivity of retinal ganglion cells is lost in the absence of melanopsin (9,11,12). Melanopsin forms a functional photopigment when heterologously expressed in COS cells (13), Xenopus oocytes (14), Neuro-2A cells (15), or HEK-293 cells (16). Melanopsin is thus necessary for ipRGC photoreception, and is sufficient to confer photosensitivity on intrinsically insensitive cell types.…”