Invertebrate Photoreceptors Research Articles

Transduction and Adaptation Mechanisms in the Cilium or Microvilli of Photoreceptors and Olfactory Receptors From Insects to Humans.

Sensing changes in the environment is crucial for survival. Animals from invertebrates to vertebrates use both visual and olfactory stimuli to direct survival behaviors including identification of food sources, finding mates, and predator avoidance. In primary sensory neurons there are signal transduction mechanisms that convert chemical or light signals into an electrical response through ligand binding or photoactivation of a receptor, that can be propagated to the olfactory and visual centers of the brain to create a perception of the odor and visual landscapes surrounding us. The fundamental principles of olfactory and phototransduction pathways within vertebrates are somewhat analogous. Signal transduction in both systems takes place in the ciliary sub-compartments of the sensory cells and relies upon the activation of G protein-coupled receptors (GPCRs) to close cyclic nucleotide-gated (CNG) cation channels in photoreceptors to produce a hyperpolarization of the cell, or in olfactory sensory neurons open CNG channels to produce a depolarization. However, while invertebrate phototransduction also involves GPCRs, invertebrate photoreceptors can be either ciliary and/or microvillar with hyperpolarizing and depolarizing responses to light, respectively. Moreover, olfactory transduction in invertebrates may be a mixture of metabotropic G protein and ionotropic signaling pathways. This review will highlight differences of the visual and olfactory transduction mechanisms between vertebrates and invertebrates, focusing on the implications to the gain of the transduction processes, and how they are modulated to allow detection of small changes in odor concentration and light intensity over a wide range of background stimulus levels.

Light control of G protein signaling pathways by a novel photopigment.

Channelopsins and photo-regulated ion channels make it possible to use light to control electrical activity of cells. This powerful approach has lead to a veritable explosion of applications, though it is limited to changing membrane voltage of the target cells. An enormous potential could be tapped if similar opto-genetic techniques could be extended to the control of chemical signaling pathways. Photopigments from invertebrate photoreceptors are an obvious choice—as they do not bleach upon illumination -however, their functional expression has been problematic. We exploited an unusual opsin, pScop2, recently identified in ciliary photoreceptors of scallop. Phylogenetically, it is closer to vertebrate opsins, and offers the advantage of being a bi-stable photopigment. We inserted its coding sequence and a fluorescent protein reporter into plasmid vectors and demonstrated heterologous expression in various mammalian cell lines. HEK 293 cells were selected as a heterologous system for functional analysis, because wild type cells displayed the largest currents in response to the G-protein activator, GTP-γ-S. A line of HEK cells stably transfected with pScop2 was generated; after reconstitution of the photopigment with retinal, light responses were obtained in some cells, albeit of modest amplitude. In native photoreceptors pScop2 couples to Go; HEK cells express poorly this G-protein, but have a prominent Gq/PLC pathway linked to internal Ca mobilization. To enhance pScop2 competence to tap into this pathway, we swapped its third intracellular loop—important to confer specificity of interaction between 7TMDRs and G-proteins—with that of a Gq-linked opsin which we cloned from microvillar photoreceptors present in the same retina. The chimeric construct was evaluated by a Ca fluorescence assay, and was shown to mediate a robust mobilization of internal calcium in response to illumination. The results project pScop2 as a potentially powerful optogenetic tool to control signaling pathways.

Giving invertebrates an eye exam: an ophthalmoscope that utilizes the autofluorescence of photoreceptors.

One of the most important functional features of eyes is focusing light, as both nearsightedness and farsightedness have major functional implications. Accordingly, refractive errors are frequently assessed in vertebrates, but not in the very small invertebrate eyes. We describe a micro-ophthalmoscope that takes advantage of autofluorescent properties of invertebrate photoreceptors and test the device on the relatively well-understood eyes of jumping spiders and flies. In each case, our measurements confirmed previous findings with a greater degree of accuracy. For example, we could precisely resolve the layering of the anterior median eyes and could map out the extensive retina of the anterior lateral eyes of the spider. Measurements also confirmed that fly ommatidia are focused into infinity, but showed that their focal plane is situated slightly below the receptor surface. In contrast to other approaches, this device does not rely on reflective tapeta and allows for precise optical assessment of diverse invertebrate eyes.

Current advances in invertebrate vision: insights from patch-clamp studies of photoreceptors in apposition eyes.

Traditional electrophysiological research on invertebrate photoreceptors has been conducted in vivo, using intracellular recordings from intact compound eyes. The only exception used to be Drosophila melanogaster, which was exhaustively studied by both intracellular recording and patch-clamp methods. Recently, several patch-clamp studies have provided new information on the biophysical properties of photoreceptors of diverse insect species, having both apposition and neural superposition eyes, in the contexts of visual ecology, behavior, and ontogenesis. Here, I discuss these and other relevant results, emphasizing differences between fruit flies and other species, between photoreceptors of diurnal and nocturnal insects, properties of distinct functional types of photoreceptors, postembryonic developmental changes, and relationships between voltage-gated potassium channels and visual ecology.

Evolutionary Characterization of the Retinitis Pigmentosa GTPase Regulator Gene.

The evolutionary conservation of the retinitis pigmentosa GTPase regulator (RPGR) gene was examined across vertebrate and invertebrate lineages to elucidate its function. Orthologous RPGR sequences from vertebrates and invertebrates were selected. Multiple sequence alignments, phylogenetic analyses, synteny, and gene structure comparisons were carried out. Expression of the alternatively spliced constitutive (RPGR(const) or RPGR(ex1-19)) and RPGR(ORF15) isoforms was examined in developing and adult zebrafish. Phylogenetic analyses and syntenic relationships were consistent with the selected sequences being true orthologues, although whole genome duplications in teleost fish resulted in a more complex picture. The splice form RPGR(const) was present in all vertebrate and invertebrate species but the defining carboxyl (C)-terminal exon of RPGR(ORF15) was absent from all invertebrates. The regulator of chromosome condensation (RCC1)-like domain adopts a seven-bladed β-propeller structure, which was present in both major splice forms and strongly conserved across evolution. The repetitive acidic region of RPGR(ORF15) showed a high rate of in-frame deletions/insertions across nine primate species, compared with flanking sequences, consistent with an unstable and rapidly evolving region. In zebrafish, RPGR(const) transcripts were most strongly expressed in early development, while the RPGR(ORF15) isoform showed highest expression in adult eye. The regulator of chromosome condensation 1-like domain of RPGR was conserved in vertebrates and invertebrates, but RPGR(ORF15) was unique to vertebrates, consistent with a proposed role in the ciliary-based transport of cargoes such as rhodopsin, which is ∼10 times more abundant in vertebrate than invertebrate photoreceptors. The repetitive acidic region of RPGR(ORF15) shows a rapid rate of evolution, consistent with a mutation "hot spot."

Electroretinogram (ERG) Recordings from Drosophila.

Phototransduction is a process in which light is converted into electrical signals used by the central nervous system. Invertebrate phototransduction is a process mediated by the phosphoinositide signaling cascade, characterized by Phospholipase C (PLC) as the effector enzyme and the Transient Receptor Potential (TRP) channels as its target. The great advantage of using invertebrate photoreceptors is the simplicity of the preparation, the ease of light stimulation, the robust expression of key molecular components, and most importantly, the ability to apply the power of molecular genetics. This last feature is mainly attributed to Drosophila melanogaster as a preferred animal model. The Electroretinogram (ERG) is an extracellular voltage recording from the entire eye, which reflects the total electrical activity arising from the retina in response to a light stimulation. The Drosophila ERG light response is robust and easily obtained, thus making it a convenient method to identify defects in the light response as a result of mutations. The Prolonged Depolarizing Afterpotential (PDA) is a useful ERG phenomenon that can be recorded from white-eyed flies following intense blue light. It is induced by a massive photo-conversion of the photopigment rhodopsin to its dark stable state called metarhodopsin, due to failure of light response termination. Unlike the light coincident ERG recording, which declines quickly to the dark baseline after the cessation of the light stimulus, the PDA response continues long (hours) after light offset. However, this response can be suppressed to the dark baseline at any time by photo-conversion of metarhodopsin back to rhodopsin, by application of an intense orange light stimulus (see Figure 7; Minke, 2012). The PDA has been used as an important tool to screen for visual defective mutant (Minke, 2012).

Developmental changes in biophysical properties of photoreceptors in the common water strider (Gerris lacustris): better performance at higher cost.

Although the dependence of invertebrate photoreceptor biophysical properties on visual ecology has already been investigated in some cases, developmental aspects have largely been ignored due to the general research emphasis on holometabolous insects. Here, using the patch-clamp method, we examined changes in biophysical properties and performance of photoreceptors in the common water strider Gerris lacustris during postembryonic development. We identified two types of peripheral photoreceptors, green and blue sensitive. Whole cell capacitance (a measure of cell size) of blue photoreceptors was significantly higher than the capacitance of green photoreceptors (69 ± 20 vs. 43 ± 12 pF, respectively). Most of the measured morphological and biophysical parameters changed with development. Photoreceptor capacitance increased progressively and was positively correlated with sensitivity to light, magnitudes and densities of light-induced (LIC) and delayed rectifier K(+) (IDR) currents, membrane corner frequency, and maximal information rate [Spearman rank correlation coefficients: 0.70 (sensitivity), 0.79 (LIC magnitude), 0.79 (IDR magnitude), 0.48 (corner frequency), and 0.57 (information rate)]. Transient K(+) current increased to a smaller extent, while its density decreased. We found no significant changes in the properties of single photon responses or levels of light-induced depolarization, the latter indicating a balanced channelome expansion associated with IDR expression. However, the dramatic ∼7.6-fold increase in IDR from first instars to adults indicated a development-related rise in the metabolic cost of information. In conclusion, this study provides novel insights into functional photoreceptor adaptations with development and illustrates remarkable variability in patterns of postembryonic retinal development in hemimetabolous insects with dissimilar visual ecologies and behaviors.

Transcriptome Analysis of Nautilus and Pygmy Squid Developing Eye Provides Insights in Lens and Eye Evolution

Coleoid cephalopods like squids have a camera-type eye similar to vertebrates. On the other hand, Nautilus (Nautiloids) has a pinhole eye that lacks lens and cornea. Since pygmy squid and Nautilus are closely related species they are excellent model organisms to study eye evolution. Having being able to collect Nautilus embryos, we employed next-generation RNA sequencing using Nautilus and pygmy squid developing eyes. Their transcriptomes were compared and analyzed. Enrichment analysis of Gene Ontology revealed that contigs related to nucleic acid binding were largely up-regulated in squid, while the ones related to metabolic processes and extracellular matrix-related genes were up-regulated in Nautilus. These differences are most likely correlated with the complexity of tissue organization in these species. Moreover, when the analysis focused on the eye-related contigs several interesting patterns emerged. First, contigs from both species related to eye tissue differentiation and morphogenesis as well as to cilia showed best hits with their Human counterparts, while contigs related to rabdomeric photoreceptors showed the best hit with their Drosophila counterparts. This bolsters the idea that eye morphogenesis genes have been generally conserved in evolution, and compliments other studies showing that genes involved in photoreceptor differentiation clearly follow the diversification of invertebrate (rabdomeric) and vertebrate (ciliated) photoreceptors. Interestingly some contigs showed as good a hit with Drosophila and Human homologues in Nautilus and squid samples. One of them, capt/CAP1, is known to be preferentially expressed in Drosophila developing eye and in vertebrate lens. Importantly our analysis also provided evidence of gene duplication and diversification of their function in both species. One of these genes is the Neurofibromatosis 1 (NF1/Nf1), which in mice has been implicated in lens formation, suggesting a hitherto unsuspected role in the evolution of the lens in molluscs.

Dissecting the Determinants of Light Sensitivity in Amphioxus Microvillar Photoreceptors: Possible Evolutionary Implications for Melanopsin Signaling

Melanopsin, a photopigment related to the rhodopsin of microvillar photoreceptors of invertebrates, evolved in vertebrates to subserve nonvisual light-sensing functions, such as the pupillary reflex and entrainment of circadian rhythms. However, vertebrate circadian receptors display no hint of a microvillar specialization and show an extremely low light sensitivity and sluggish kinetics. Recently in amphioxus, the most basal chordate, melanopsin-expressing photoreceptors were characterized; these cells share salient properties with both rhabdomeric photoreceptors of invertebrates and circadian receptors of vertebrates. We used electrophysiology to dissect the gain of the light-transduction process in amphioxus and examine key features that help outline the evolutionary transition toward a sensor optimized to report mean ambient illumination rather than mediating spatial vision. By comparing the size of current fluctuations attributable to single photon melanopsin isomerizations with the size of single-channels activated by light, we concluded that the gain of the transduction cascade is lower than in rhabdomeric receptors. In contrast, the expression level of melanopsin (gauged by measuring charge displacements during photo-induced melanopsin isomerization) is comparable with that of canonical visual receptors. A modest amplification in melanopsin-using receptors is therefore apparent in early chordates; the decrease in photopigment expression-and loss of the anatomical correlates-observed in vertebrates subsequently enabled them to attain the low photosensitivity tailored to the role of circadian receptors.

Cross species analysis of Prominin reveals a conserved cellular role in invertebrate and vertebrate photoreceptor cells

The two fundamental types of photoreceptor cells have evolved unique structures to expand the apical membrane to accommodate the phototransduction machinery, exemplified by the cilia-based outer segment of the vertebrate photoreceptor cell and the microvilli-based rhabdomere of the invertebrate photoreceptor. The morphogenesis of these compartments is integral for photoreceptor cell integrity and function. However, little is known about the elementary cellular and molecular mechanisms required to generate these compartments. Here we investigate whether a conserved cellular mechanism exists to create the phototransduction compartments by examining the functional role of a photoreceptor protein common to both rhabdomeric and ciliated photoreceptor cells, Prominin. First and foremost we demonstrate that the physiological role of Prominin is conserved between rhabdomeric and ciliated photoreceptor cells. Human Prominin1 is not only capable of rescuing the corresponding rhabdomeric Drosophila prominin mutation but also demonstrates a conserved genetic interaction with a second photoreceptor protein Eyes Shut. Furthermore, we demonstrate the Prominin homologs in vertebrate and invertebrate photoreceptors require the same structural features and post-translational modifications for function. Moreover, expression of mutant human Prominin1, associated with autosomal dominant retinal degeneration, in rhabdomeric photoreceptor cells disrupts morphogenesis in ways paralleling retinal degeneration seen in ciliated photoreceptors. Taken together, our results suggest the existence of an ancestral Prominin-directed cellular mechanism to create and model the apical membranes of the two fundamental types of photoreceptor cells into their respective phototransduction compartments.

Melanopsin, the photopigment of intrinsically photosensitive retinal ganglion cells

AbstractMelanopsin (gene symbol: Opn4) is the G protein‐coupled photopigment that confers photosensitivity upon intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs are the third class of retinal photoreceptor in mammals, complementing the two previously identified classes, the rods and cones. This novel class, however, differs from rods and cones in many significant ways. First, ipRGCs are more similar morphologically to other retinal ganglion cell classes than to other retinal photoreceptors, i.e., rods and cones. Instead of having photopigment concentrated in a specialized light‐absorbing cellular domain such as the outer segment, ipRGCs have photopigment distributed throughout the plasma membrane of the cell. Second, the phototransduction cascade of ipRGCs more closely resembles that of the rhabdomeric photoreceptors that are typically found in the invertebrates rather than that of ciliary photoreceptors typical of vertebrate visual systems. Accordingly, like the rhabdomeric photoreceptors of invertebrates, ipRGCs depolarize in response to illumination while rods and cones hyperpolarize. Third, in addition to their inherent light sensitivity, ipRGCs also function as a conduit for information that originates in the rods and cones and is conveyed to the brain for the purposes of generating non‐visual light responses. WIREs Membr Transp Signal 2012, 1:228–237. doi: 10.1002/wmts.29For further resources related to this article, please visit the WIREs website.

XPORT-Dependent Transport of TRP and Rhodopsin

TRP channels have emerged as key biological sensors in vision, taste, olfaction, hearing, and touch. Despite their importance, virtually nothing is known about the folding and transport of TRP channels during biosynthesis. Here, we identify XPORT (exit protein of rhodopsin and TRP) as a critical chaperone for TRP and its G protein-coupled receptor (GPCR), rhodopsin (Rh1). XPORT is a resident ER and secretory pathway protein that interacts with TRP and Rh1, as well as with Hsp27 and Hsp90. XPORT promotes the targeting of TRP to the membrane in Drosophila S2 cells, a finding that provides a critical first step toward solving a longstanding problem inthe successful heterologous expression of TRP. Mutations in xport result in defective transport of TRP and Rh1, leading to retinal degeneration. Our results identify XPORT as a molecular chaperone and provide a mechanistic link between TRP channels and their GPCRs during biosynthesis and transport.

Arrestin in Ciliary Invertebrate Photoreceptors: Molecular Identification and Functional AnalysisIn Vivo

Arrestin was identified in ciliary photoreceptors of Pecten irradians, and its role in terminating the light response was established electrophysiologically. Downstream effectors in these unusual visual cells diverge from both microvillar photoreceptors and rods and cones; the finding that key regulatory mechanisms of the early steps of visual excitation are conserved across such distant lineages of photoreceptors underscores that a common blueprint for phototransduction exists across metazoa. Arrestin was detected by Western blot analysis of retinal lysates, and localized in ciliary photoreceptors by immunostaining of whole-eye cryosections and dissociated cells. Two arrestin isoforms were molecularly identified by PCR; these present the canonical N- and C-arrestin domains, and are identical at the nucleotide level over much of their sequence. A high degree of homology to various β-arrestins (up to 70% amino acid identity) was found. In situ hybridization localized the two transcripts within the retina, but failed to reveal finer spatial segregation, possibly because of insufficient differences between the riboprobes. Intracellular dialysis of anti arrestin antibodies into voltage-clamped ciliary photoreceptors produced a gradual slow-down of the photocurrent falling phase, leaving a tail that decayed over many seconds after light termination. The antibodies also caused spectrally neutral flashes to elicit prolonged aftercurrents in the absence of large metarhodopsin accumulation; such aftercurrents could be quenched by chromatic illumination that photoconverts metarhodopsin back to rhodopsin. These observations indicate that the antibodies depleted functionally available arrestin, and implicate this molecule in the deactivation of the photoresponse at the rhodopsin level.

Metarhodopsin control by arrestin, light-filtering screening pigments, and visual pigment turnover in invertebrate microvillar photoreceptors.

The visual pigments of most invertebrate photoreceptors have two thermostable photo-interconvertible states, the ground state rhodopsin and photo-activated metarhodopsin, which triggers the phototransduction cascade until it binds arrestin. The ratio of the two states in photoequilibrium is determined by their absorbance spectra and the effective spectral distribution of illumination. Calculations indicate that metarhodopsin levels in fly photoreceptors are maintained below ~35% in normal diurnal environments, due to the combination of a blue-green rhodopsin, an orange-absorbing metarhodopsin and red transparent screening pigments. Slow metarhodopsin degradation and rhodopsin regeneration processes further subserve visual pigment maintenance. In most insect eyes, where the majority of photoreceptors have green-absorbing rhodopsins and blue-absorbing metarhodopsins, natural illuminants are predicted to create metarhodopsin levels greater than 60% at high intensities. However, fast metarhodopsin decay and rhodopsin regeneration also play an important role in controlling metarhodopsin in green receptors, resulting in a high rhodopsin content at low light intensities and a reduced overall visual pigment content in bright light. A simple model for the visual pigment–arrestin cycle is used to illustrate the dependence of the visual pigment population states on light intensity, arrestin levels and pigment turnover.

Prolonged calcium influx after termination of light-induced calcium release in invertebrate photoreceptors

In microvillar photoreceptors, light stimulates the phospholipase C cascade and triggers an elevation of cytosolic Ca2+ that is essential for the regulation of both visual excitation and sensory adaptation. In some organisms, influx through light-activated ion channels contributes to the Ca2+ increase. In contrast, in other species, such as Lima, Ca2+ is initially only released from an intracellular pool, as the light-sensitive conductance is negligibly permeable to calcium ions. As a consequence, coping with sustained stimulation poses a challenge, requiring an alternative pathway for further calcium mobilization. We observed that after bright or prolonged illumination, the receptor potential of Lima photoreceptors is followed by the gradual development of an after-depolarization that decays in 1–4 minutes. Under voltage clamp, a graded, slow inward current (Islow) can be reproducibly elicited by flashes that saturate the photocurrent, and can reach a peak amplitude in excess of 200 pA. Islow obtains after replacing extracellular Na+ with Li+, guanidinium, or N-methyl-d-glucamine, indicating that it does not reflect the activation of an electrogenic Na/Ca exchange mechanism. An increase in membrane conductance accompanies the slow current. Islow is impervious to anion replacements and can be measured with extracellular Ca2+ as the sole permeant species; Ba can substitute for Ca2+ but Mg2+ cannot. A persistent Ca2+ elevation parallels Islow, when no further internal release takes place. Thus, this slow current could contribute to sustained Ca2+ mobilization and the concomitant regulation of the phototransduction machinery. Although reminiscent of the classical store depletion–operated calcium influx described in other cells, Islow appears to diverge in some significant aspects, such as its large size and insensitivity to SKF96365 and lanthanum; therefore, it may reflect an alternative mechanism for prolonged increase of cytosolic calcium in photoreceptors.

Melanopsin Bistability: A Fly's Eye Technology in the Human Retina

In addition to rods and cones, the human retina contains light-sensitive ganglion cells that express melanopsin, a photopigment with signal transduction mechanisms similar to that of invertebrate rhabdomeric photopigments (IRP). Like fly rhodopsins, melanopsin acts as a dual-state photosensitive flip-flop in which light drives both phototransduction responses and chromophore photoregeneration that bestows independence from the retinoid cycle required by rods and cones to regenerate photoresponsiveness following bleaching by light. To explore the hypothesis that melanopsin in humans expresses the properties of a bistable photopigment in vivo we used the pupillary light reflex (PLR) as a tool but with methods designed to study invertebrate photoreceptors. We show that the pupil only attains a fully stabilized state of constriction after several minutes of light exposure, a feature that is consistent with typical IRP photoequilibrium spectra. We further demonstrate that previous exposure to long wavelength light increases, while short wavelength light decreases the amplitude of pupil constriction, a fundamental property of IRP difference spectra. Modelling these responses to invertebrate photopigment templates yields two putative spectra for the underlying R and M photopigment states with peaks at 481 nm and 587 nm respectively. Furthermore, this bistable mechanism may confer a novel form of “photic memory” since information of prior light conditions is retained and shapes subsequent responses to light. These results suggest that the human retina exploits fly-like photoreceptive mechanisms that are potentially important for the modulation of non-visual responses to light and highlights the ubiquitous nature of photoswitchable photosensors across living organisms.

Systems analysis of the single photon response in invertebrate photoreceptors

Photoreceptors of Drosophila compound eye employ a G protein-mediated signaling pathway that transduces single photons into transient electrical responses called "quantum bumps" (QB). Although most of the molecular components of this pathway are already known, the system-level understanding of the mechanism of QB generation has remained elusive. Here, we present a quantitative model explaining how QBs emerge from stochastic nonlinear dynamics of the signaling cascade. The model shows that the cascade acts as an "integrate and fire" device and explains how photoreceptors achieve reliable responses to light although keeping low background in the dark. The model predicts the nontrivial behavior of mutants that enhance or suppress signaling and explains the dependence on external calcium, which controls feedback regulation. The results provide insight into physiological questions such as single-photon response efficiency and the adaptation of response to high incident-light level. The system-level analysis enabled by modeling phototransduction provides a foundation for understanding G protein signaling pathways less amenable to quantitative approaches.

The rhodopsin story continued

Determination of the architecture of an invertebrate photoreceptor protein, squid rhodopsin, is a notable event. It illuminates the mechanism of invertebrate vision and a ubiquitous intracellular signalling system.

Translocation of Gqα Mediates Long-Term Adaptation inDrosophilaPhotoreceptors

Light adaptation is a process that enables photoreceptor cells to operate over a wide range of light intensities without saturation. In invertebrate photoreceptors, fast adaptation is mediated by a Ca2+-dependent negative-feedback mechanism, which mainly affects the terminal steps of the cascade. Therefore, the response to each photon is smaller as light intensity increases, accommodating both high sensitivity and a vast dynamic range. Here, we describe a novel type of adaptation, which is mediated by one of the first steps in the phototransduction cascade affecting the sensitivity to absorbed photons. Long exposure to light resulted in dramatic reduction in the probability of each absorbed photon to elicit a response, whereas the size and shape of each single photon response did not change. To dissect the molecular mechanism underlying this form of adaptation we used a series of Drosophila mutants. Genetic dissection showed a pivotal role for light-induced translocation of Gq alpha between the signaling membrane and the cytosol. Biochemical studies revealed that the sensitivity to light depends on membrane Gq alpha concentration, which was modulated either by light or by mutations that impaired its targeting to the membrane. We conclude that long-term adaptation is mediated by the movement of Gq alpha from the signaling membrane to the cytosol, thereby reducing the probability of each photon to elicit a response. The slow time scale of this adaptation fits well with day/night light intensity changes, because there is no need to maintain single photon sensitivity during daytime.

Phototransduction in ganglion-cell photoreceptors

A third class of photoreceptors has recently been identified in the mammalian retina. They are a rare cell type within the class of ganglion cells, which are the output cells of the retina. These intrinsically photosensitive retinal ganglion cells support a variety of physiological responses to daylight, including synchronization of circadian rhythms, modulation of melatonin release, and regulation of pupil size. The goal of this review is to summarize what is currently known concerning the cellular and biochemical basis of phototransduction in these cells. I summarize the overwhelming evidence that melanopsin serves as the photopigment in these cells and review the emerging evidence that the downstream signaling cascade, including the light-gated channel, might resemble those found in rhabdomeric invertebrate photoreceptors.