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Progress in Retinal and Eye Research Sep 2012The light responses of rod and cone photoreceptors in the vertebrate retina are quantitatively different, yet extremely stable and reproducible because of the... (Review)
Review
The light responses of rod and cone photoreceptors in the vertebrate retina are quantitatively different, yet extremely stable and reproducible because of the extraordinary regulation of the cascade of enzymatic reactions that link photon absorption and visual pigment excitation to the gating of cGMP-gated ion channels in the outer segment plasma membrane. While the molecular scheme of the phototransduction pathway is essentially the same in rods and cones, the enzymes and protein regulators that constitute the pathway are distinct. These enzymes and regulators can differ in the quantitative features of their functions or in concentration if their functions are similar or both can be true. The molecular identity and distinct function of the molecules of the transduction cascade in rods and cones are summarized. The functional significance of these molecular differences is examined with a mathematical model of the signal-transducing enzymatic cascade. Constrained by available electrophysiological, biochemical and biophysical data, the model simulates photocurrents that match well the electrical photoresponses measured in both rods and cones. Using simulation computed with the mathematical model, the time course of light-dependent changes in enzymatic activities and second messenger concentrations in non-mammalian rods and cones are compared side by side.
Topics: Adaptation, Ocular; Animals; Calcium; Guanylate Cyclase-Activating Proteins; Humans; Ion Channels; Models, Animal; Models, Biological; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rod Cell Outer Segment; Signal Transduction
PubMed: 22658984
DOI: 10.1016/j.preteyeres.2012.05.002 -
Current Biology : CB Sep 1999
Review
Topics: Animals; Contrast Sensitivity; Humans; Ion Transport; Light; Membrane Potentials; Mice; Mice, Transgenic; Neurotransmitter Agents; Retina; Retinal Ganglion Cells; Retinal Rod Photoreceptor Cells; Rhodopsin; Signal Transduction; Synaptic Transmission; Vision, Ocular; Visual Pathways
PubMed: 10508621
DOI: 10.1016/s0960-9822(99)80436-9 -
The Journal of Neuroscience : the... Jan 2007The Akt kinases mediate cell survival through phosphorylation and inactivation of apoptotic machinery components. Akt signaling provides a trophic signal for transformed...
The Akt kinases mediate cell survival through phosphorylation and inactivation of apoptotic machinery components. Akt signaling provides a trophic signal for transformed retinal neurons in culture, but the in vivo role of Akt activity is unknown. In this study, we found that all three Akt isoforms were expressed in rod photoreceptor cells. We investigated the functional roles of Akt1 and Akt2, two of the isoforms of Akt, and their biological significance in light-induced retinal degeneration. Consistent with the hypothesis that Akt activity is important to circumvent stress-induced apoptosis, herein we report the novel finding that rod photoreceptor cells in Akt2 knock-out mice exhibited a significantly greater sensitivity to stress-induced cell death than rods in heterozygous or wild-type mice. Under similar conditions, Akt1 deletion had no effect on the retina. The presence of three Akt isoforms in the retina is suggestive of a functional redundancy; however, our studies clearly demonstrate that, under stress, Akt1 and Akt3 cannot complement the specific survival signals driven by Akt2. Furthermore, we show that Akt2 is specially activated is response to light stress. The results presented in this study provide the first direct evidence that Akt2 has a nonredundant neuroprotective role in photoreceptor survival and maintenance.
Topics: Animals; Apoptosis; Dose-Response Relationship, Radiation; Light; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuroprotective Agents; Proto-Oncogene Proteins c-akt; Radiation Dosage; Retinal Rod Photoreceptor Cells
PubMed: 17202487
DOI: 10.1523/JNEUROSCI.0445-06.2007 -
Cell Motility and the Cytoskeleton Oct 2008In vertebrate rod photoreceptor cells, arrestin and the visual G-protein transducin move between the inner segment and outer segment in response to changes in light....
In vertebrate rod photoreceptor cells, arrestin and the visual G-protein transducin move between the inner segment and outer segment in response to changes in light. This stimulus dependent translocation of signalling molecules is assumed to participate in long term light adaptation of photoreceptors. So far the cellular basis for the transport mechanisms underlying these intracellular movements remains largely elusive. Here we investigated the dependency of these movements on actin filaments and the microtubule cytoskeleton of photoreceptor cells. Co-cultures of mouse retina and retinal pigment epithelium were incubated with drugs stabilizing and destabilizing the cytoskeleton. The actin and microtubule cytoskeleton and the light dependent distribution of signaling molecules were subsequently analyzed by light and electron microscopy. The application of cytoskeletal drugs differentially affected the cytoskeleton in photoreceptor compartments. During dark adaptation the depolymerization of microtubules as well as actin filaments disrupted the translocation of arrestin and transducin in rod photoreceptor cells. During light adaptation only the delivery of arrestin within the outer segment was impaired after destabilization of microtubules. Movements of transducin and arrestin required intact cytoskeletal elements in dark adapting cells. However, diffusion might be sufficient for the fast molecular movements observed as cells adapt to light. These findings indicate that different molecular translocation mechanisms are responsible for the dark and light associated translocations of arrestin and transducin in rod photoreceptor cells.
Topics: Actin Cytoskeleton; Actins; Animals; Arrestin; Cell Migration Assays; Cytochalasin D; Cytoskeleton; Dark Adaptation; Darkness; Heterocyclic Compounds, 4 or More Rings; Homozygote; Light; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Fluorescence; Microscopy, Immunoelectron; Microtubules; Paclitaxel; Phalloidine; Protein Transport; Retina; Retinal Rod Photoreceptor Cells; Rod Cell Outer Segment; Signal Transduction; Thiabendazole; Transducin; Vision, Ocular
PubMed: 18623243
DOI: 10.1002/cm.20300 -
The Journal of Biological Chemistry Feb 2014Most vertebrate retinas contain two types of photoreceptor cells, rods and cones, which show different photoresponses to mediate scotopic and photopic vision,... (Comparative Study)
Comparative Study
Most vertebrate retinas contain two types of photoreceptor cells, rods and cones, which show different photoresponses to mediate scotopic and photopic vision, respectively. These cells contain different types of visual pigments, rhodopsin and cone visual pigments, respectively, but little is known about the molecular properties of cone visual pigments under physiological conditions, making it difficult to link the molecular properties of rhodopsin and cone visual pigments with the differences in photoresponse between rods and cones. Here we prepared bovine and mouse rhodopsin (bvRh and mRh) and chicken and mouse green-sensitive cone visual pigments (cG and mG) embedded in nanodiscs and applied time-resolved fluorescence spectroscopy to compare their Gt activation efficiencies. Rhodopsin exhibited greater Gt activation efficiencies than cone visual pigments. Especially, the Gt activation efficiency of mRh was about 2.5-fold greater than that of mG at 37 °C, which is consistent with our previous electrophysiological data of knock-in mice. Although the active state (Meta-II) was in equilibrium with inactive states (Meta-I and Meta-III), quantitative determination of Meta-II in the equilibrium showed that the Gt activation efficiency per Meta-II of bvRh was also greater than those of cG and mG. These results indicated that efficient Gt activation by rhodopsin, resulting from an optimized active state of rhodopsin, is one of the causes of the high amplification efficiency of rods.
Topics: Animals; Cattle; Chickens; HEK293 Cells; Humans; Kinetics; Light; Mice; Retinal Cone Photoreceptor Cells; Retinal Pigments; Retinal Rod Photoreceptor Cells; Rhodopsin; Rod Cell Outer Segment; Spectrum Analysis; Transducin
PubMed: 24375403
DOI: 10.1074/jbc.M113.508507 -
Cell Death and Differentiation Mar 2015Damage and loss of the postmitotic photoreceptors is a leading cause of blindness in many diseases of the eye. Although the mechanisms of photoreceptor death have been...
Damage and loss of the postmitotic photoreceptors is a leading cause of blindness in many diseases of the eye. Although the mechanisms of photoreceptor death have been extensively studied, few studies have addressed mechanisms that help sustain these non-replicating neurons for the life of an organism. Autophagy is an intracellular pathway where cytoplasmic constituents are delivered to the lysosomal pathway for degradation. It is not only a major pathway activated in response to cellular stress, but is also important for cytoplasmic turnover and to supply the structural and energy needs of cells. We examined the importance of autophagy in photoreceptors by deleting the essential autophagy gene Atg5 specifically in rods. Loss of autophagy led to progressive degeneration of rod photoreceptors beginning at 8 weeks of age such that by 44 weeks few rods remained. Cone photoreceptor numbers were only slightly diminished following rod degeneration but their function was significantly decreased. Rod cell death was apoptotic but was not dependent on daily light exposure or accelerated by intense light. Although the light-regulated translocation of the phototransduction proteins arrestin and transducin were unaffected in rods lacking autophagy, Atg5-deficient rods accumulated transducin-α as they degenerated suggesting autophagy might regulate the level of this protein. This was confirmed when the light-induced decrease in transducin was abolished in Atg5-deficient rods and the inhibition of autophagy in retinal explants cultures prevented its degradation. These results demonstrate that basal autophagy is essential to the long-term health of rod photoreceptors and a critical process for maintaining optimal levels of the phototransduction protein transducin-α. As the lack of autophagy is associated with retinal degeneration and altered phototransduction protein degradation in the absence of harmful gene products, this process may be a viable therapeutic target where rod cell loss is the primary pathologic event.
Topics: Animals; Autophagy; Autophagy-Related Protein 5; Light Signal Transduction; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microtubule-Associated Proteins; Retinal Rod Photoreceptor Cells; Survival Analysis
PubMed: 25571975
DOI: 10.1038/cdd.2014.229 -
Experimental Eye Research Aug 1993The chicken retina has several types of cone photoreceptor cells, each of which contains a visual pigment, chicken red (iodopsin), green, blue or violet. Although...
The chicken retina has several types of cone photoreceptor cells, each of which contains a visual pigment, chicken red (iodopsin), green, blue or violet. Although biochemical and photochemical properties of these cone pigments have been well characterized, no information is available about the chicken photoreceptor G-protein, transducin, which couples with the visual pigment to convert a photon signal into a cellular response. To identify alpha-subunits of chicken rod and cone transducins (Tr alpha and Tc alpha, respectively), we produced two site-directed antibodies which discriminate between bovine Tr alpha and Tc alpha. Immunohistochemical studies on chicken retinas revealed that the antibody against bovine Tr alpha specifically stained the rod outer segments. On the other hand, the antibody against bovine Tc alpha uniformly stained the outer segments of the double cones and all types of single cones, while the single cones were immunohistochemically classified into three types by using a combination of antibodies against bovine rhodopsin and chicken iodopsin. Immuno-blot analyses demonstrated that the antibody against Tc alpha recognized a single band of chicken photoreceptor protein, whose molecular weight (42,000) was in good agreement with that of bovine Tc alpha (41,000). The antibody against Tr alpha recognized a protein having the same molecular weight as that of bovine Tr alpha (39,000). These observations strongly suggested that all types of chicken cone cells have a single common Tc alpha (42 kDa) structurally related to bovine Tc alpha, though each cone cell type has a distinct visual pigment.
Topics: Animals; Chickens; Immunoblotting; Immunohistochemistry; Molecular Weight; Retinal Rod Photoreceptor Cells; Rod Cell Outer Segment; Transducin
PubMed: 8405179
DOI: 10.1006/exer.1993.1108 -
Proceedings of the National Academy of... Feb 2020Rod and cone photoreceptor outer segment (OS) structural integrity is essential for normal vision; disruptions contribute to a broad variety of retinal ciliopathies. OSs...
Rod and cone photoreceptor outer segment (OS) structural integrity is essential for normal vision; disruptions contribute to a broad variety of retinal ciliopathies. OSs possess many hundreds of stacked membranous disks, which capture photons and scaffold the phototransduction cascade. Although the molecular basis of OS structure remains unresolved, recent studies suggest that the photoreceptor-specific tetraspanin, peripherin-2/rds (P/rds), may contribute to the highly curved rim domains at disk edges. Here, we demonstrate that tetrameric P/rds self-assembly is required for generating high-curvature membranes in cellulo, implicating the noncovalent tetramer as a minimal unit of function. P/rds activity was promoted by disulfide-mediated tetramer polymerization, which transformed localized regions of curvature into high-curvature tubules of extended lengths. Transmission electron microscopy visualization of P/rds purified from OS membranes revealed disulfide-linked tetramer chains up to 100 nm long, suggesting that chains maintain membrane curvature continuity over extended distances. We tested this idea in photoreceptors, and found that transgenic expression of nonchain-forming P/rds generated abundant high-curvature OS membranes, which were improperly but specifically organized as ectopic incisures and disk rims. These striking phenotypes demonstrate the importance of P/rds tetramer chain formation for the continuity of rim formation during disk morphogenesis. Overall, this study advances understanding of the normal structure and function of P/rds for OS architecture and biogenesis, and clarifies how pathogenic loss-of-function mutations in P/rds cause photoreceptor structural defects to trigger progressive retinal degenerations. It also introduces the possibility that other tetraspanins may generate or sense membrane curvature in support of diverse biological functions.
Topics: Animals; Humans; Peripherins; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rod Cell Outer Segment; Xenopus laevis
PubMed: 32041874
DOI: 10.1073/pnas.1912513117 -
Neuron May 2001
Review
Topics: Animals; Humans; Neurons; Photoreceptor Cells, Vertebrate; Pigment Epithelium of Eye; Retina; Retinal Rod Photoreceptor Cells; Sodium Channels; Vertebrates
PubMed: 11394991
DOI: 10.1016/s0896-6273(01)00308-7 -
Trends in Neurosciences Mar 2002Rhodopsin phosphorylation has provided one of the first examples of the ubiquitous regulatory pattern of specific kinases downregulating the activity of... (Review)
Review
Rhodopsin phosphorylation has provided one of the first examples of the ubiquitous regulatory pattern of specific kinases downregulating the activity of G-protein-coupled receptors. However, only recently have studies in living animals allowed us to consider the role of rhodopsin phosphorylation in a broader spectrum of visual functions, ranging from the ability of rods to generate reproducible electrical responses to their ability to adapt to darkness after substantial light exposures.
Topics: Animals; Arrestin; Cell Membrane; Dark Adaptation; Eye Proteins; G-Protein-Coupled Receptor Kinase 1; Humans; Phosphorylation; Protein Kinases; Retinal Rod Photoreceptor Cells; Rhodopsin; Vision, Ocular
PubMed: 11852136
DOI: 10.1016/s0166-2236(00)02094-4