Search results for "Opsin"
showing 10 items of 95 documents
Induced Night-Vision by Singlet-Oxygen-Mediated Activation of Rhodopsin
2019
In humans, vision is limited to a small fraction of the whole electromagnetic spectrum. One possible strategy for enhancing vision in deep-red or poor-light conditions consists of recruiting chlorophyll derivatives in the rod photoreceptor cells of the eye, as suggested in the case of some deep-sea fish. Here, we employ all-atom molecular simulations and high-level quantum chemistry calculations to rationalize how chlorin e6 (Ce6), widely used in photodynamic therapy although accompanied by enhanced visual sensitivity, mediates vision in the dark, shining light on a fascinating but largely unknown molecular mechanism. First, we identify persistent interaction sites between Ce6 and the extra…
Rhodopsin transport in the membrane of the connecting cilium of mammalian photoreceptor cells
2000
The transport of the photopigment rhodopsin from the inner segment to the photosensitive outer segment of vertebrate photoreceptor cells has been one of the main remaining mysteries in photoreceptor cell biology. Because of the lack of any direct evidence for the pathway through the photoreceptor cilium, alternative extracellular pathways have been proposed. Our primary aim in the present study was to resolve rhodopsin trafficking from the inner to the outer segment. We demonstrate, predominantly by high-sensitive immunoelectron microscopy, that rhodopsin is also densely packed in the membrane of the photoreceptor connecting cilium. Present prominent labeling of rhodopsin in the ciliary mem…
Effect of opsin on the shape of the potential energy surfaces at the conical intersection of the Rhodopsin chromophore
2008
Abstract In order to disentangle the role of the protein in the control of the photoisomerization of the chromophore of the visual pigment Rhodopsin, we compare the structure of the ground and excited potential energy surfaces of gas-phase and opsin-embedded 11- cis retinal chromophore at the corresponding (lowest energy) conical intersections. It is shown that, along the branching plane, the asymmetric opsin environment destabilizes one of the ground state relaxation channels emerging from the conical intersection. This suggests that opsin promotes the formation of the product (bathorhodopsin) via enhanced decay probability along the all- trans exit channel. In contrast, in the gas-phase n…
Disruption of the retinitis pigmentosa 28 gene Fam161a in mice affects photoreceptor ciliary structure and leads to progressive retinal degeneration.
2014
Mutations in the FAM161A gene were previously identified as the cause for autosomal-recessive retinitis pigmentosa 28. To study the effects of Fam161a dysfunction in vivo, we generated gene-trapped Fam161a(GT/GT) mice with a disruption of its C-terminal domain essential for protein-protein interactions. We confirmed the absence of the full-length Fam161a protein in the retina of Fam161a(GT/GT) mice using western blots and showed weak expression of a truncated Fam161a protein by immunohistochemistry. Histological analyses demonstrated that photoreceptor segments were disorganized in young Fam161a(GT/GT) mice and that the outer retina was completely lost at 6 months of age. Reactive microglia…
Peripherin-2 differentially interacts with cone opsins in outer segments of cone photoreceptors
2016
Peripherin-2 is a glycomembrane protein exclusively expressed in the light-sensing compartments of rod and cone photoreceptors designated as outer segments (OS). Mutations in peripherin-2 are associated with degenerative retinal diseases either affecting rod or cone photoreceptors. While peripherin-2 has been extensively studied in rods, there is only little information on its supramolecular organization and function in cones. Recently, we have demonstrated that peripherin-2 interacts with the light detector rhodopsin in OS of rods. It remains unclear, however, if peripherin-2 also binds to cone opsins. Here, using a combination of co-immunoprecipitation analyses, transmission electron micr…
Molecular genetics of autosomal dominant retinitis pigmentosa (ADRP): a comprehensive study of 43 Italian families
2005
Retinitis pigmentosa is the most common form of retinal degeneration and is heterogeneous both clinically and genetically. The autosomal dominant forms ( ADRP) can be caused by mutations in 12 different genes. This report describes the first simultaneous mutation analysis of all the known ADRP genes in the same population, represented by 43 Italian families. This analysis allowed the identification of causative mutations in 12 of the families (28% of the total). Seven different mutations were identified, two of which are novel (458delC and 6901C --> T (P2301S), in the CRX and PRPF8 genes, respectively). Several novel polymorphisms leading to amino acid changes in the FSCN2, NRL, IMPDH1, and…
Rev-Erb modulates retinal visual processing and behavioral responses to light
2016
International audience; The circadian clock is thought to adjust retinal sensitivity to ambient light levels, yet the involvement of specific clock genes is poorly understood. We explored the potential role of the nuclear receptor subfamily 1, group D, member 1 (REV-ERB; or NR1D1) in this respect. In light-evoked behavioral tests, compared with wild-type littermates, Rev-Erb(-/-) mice showed enhanced negative masking at low light levels (0.1 lx). Rev-Erb(-/-) mouse retinas displayed significantly higher numbers of intrinsically photosensitive retinal ganglion cells (ipRGCs; 62% more compared with wild-type) and more intense melanopsin immunostaining of individual ipRGCs. In agreement with a…
Synthesis of the new oligopeptide pyrrole derivative isonetropsin and its one pyrrole unit analogue
2013
We have designed and synthesized isonetropsin and its one pyrrole unit analogue in which the amine and carbonyl groups have been switched in positions 2 and 4, respectively instead of 4 and 2 positions of the natural antibiotic netropsin.
Circadian gene expression patterns of melanopsin and pinopsin in the chick pineal gland
2004
The directly light-sensitive chick pineal gland contains at least two photopigments. Pinopsin seems to mediate the acute inhibitory effect of light on melatonin synthesis, whereas melanopsin may act by phase-shifting the intrapineal circadian clock. In the present study we have investigated, by means of quantitative RT-PCR, the daily rhythm of photopigment gene expression as monitored by mRNA levels. Under a 12-h light/12-h dark cycle, the mRNA levels of both pigments were 5-fold higher in the transitional phase from light to dark than at night, both in vivo and in vitro. Under constant darkness in vivo and in vitro, the peak of pinopsin mRNA levels was attenuated, whereas that of melanopsi…
Homology models of melatonin receptors: challenges and recent advances
2013
Melatonin exerts many of its actions through the activation of two G protein-coupled receptors (GPCRs), named MT1 and MT2. So far, a number of different MT1 and MT2 receptor homology models, built either from the prototypic structure of rhodopsin or from recently solved X-ray structures of druggable GPCRs, have been proposed. These receptor models differ in the binding modes hypothesized for melatonin and melatonergic ligands, with distinct patterns of ligand-receptor interactions and putative bioactive conformations of ligands. The receptor models will be described, and they will be discussed in light of the available information from mutagenesis experiments and ligand-based pharmacophore …