Breaking the Covalent Bond— A Pigment Property that Contributes to Desensitization in Cones

Kefalov, Vladimir J.; Estevez, Maureen E.; Kono, Massahiro; Goletz, Patrice; Crouch, Rosalie K.; Cornwall, M. Carter; Yau, King Wai

doi:10.1016/j.neuron.2005.05.009

Cited by 98 publications

(130 citation statements)

References 55 publications

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“…Alternatively, they could be due to constant retinal release from the protein via cleavage of covalent bond (Schiff base linkage) with retinal. The latter possibility would be similar to what occurs in cone photoreceptor cells, where retinal is known to spontaneously dissociate from visual pigments, resulting in reduced overall cellular photosensitivity (30,31).…”

mentioning

confidence: 88%

“…We used this approach because retinal absorbance decreases after Schiff base hydrolysis (52), and this type of analysis is widely used to assess retinal-protein stability in purified rod and cone visual pigments (30,53,54).…”

Section: Xenopus Opn4xmentioning

confidence: 99%

“…7). Finally, faster retinalSchiff base linkage hydrolysis for cone visual pigments (30) and some mutants of rod visual pigments (53,56) has been determined using purified and detergent solubilized pigments. These molecular properties of the purified photopigments are found to be consistent with cellular responses expressing these pigments (see the Introduction and below) (31,59).…”

Section: Dog Opn4mentioning

confidence: 99%

“…For vertebrate visual pigments, it is well established that the retinal-free forms can constitutively activate G proteins (30, 60 -63). In cone visual cells, the light-independent G protein activation by the retinal-free protein acts to desensitize the cells by lowering their overall photosensitivity (30,31). Similarly, in rod visual cells, the constitutive G protein activity accompanying some rhodopsin mutants that exhibit faster retinal-Schiff base hydrolysis can cause night blindness by desensitization of the cells (53,59,64).…”

Section: Dog Opn4mentioning

confidence: 99%

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Retinal Attachment Instability Is Diversified among Mammalian Melanopsins

Tsukamoto

Kubo

Farrens

et al. 2015

Journal of Biological Chemistry

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Background: Melanopsin is involved in non-visual photoreception in mammals, but molecular characteristics underlying these non-visual functions are unclear. Results: Stability of the bond with the retinal chromophore is weakened and diversified in mammalian melanopsins. Conclusion: Mammalian melanopsins have acquired characteristics suited for their non-visual functions. Significance: The weaker retinal attachment in melanopsin may contribute to the functional tuning of non-visual photoreception in mammals.

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mentioning

confidence: 88%

Section: Xenopus Opn4xmentioning

confidence: 99%

Section: Dog Opn4mentioning

confidence: 99%

Section: Dog Opn4mentioning

confidence: 99%

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Retinal Attachment Instability Is Diversified among Mammalian Melanopsins

Tsukamoto

Kubo

Farrens

et al. 2015

Journal of Biological Chemistry

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“…(D) Flash families from Rho +/− and S-opsin + Rho +/− rods after 11-cis-retinal treatment. Although both rods had 11-cis-retinal throughout life, we nonetheless pretreated them with 11-cis-retinal to remove any bare opsin (42), providing a better comparison with the data presented in A-C above. A 12.1-ms flash at time 0 delivered 4.5, 7.8, 16.7, 35.7, 60.2, 115, 204, and 472 photons·μm −2 at 500 nm in both cases.…”

Section: Disruption By Helix Peptides Of R-and S-opsin Trafficking Inmentioning

confidence: 99%

Dimerization of visual pigments in vivo

Zhang

Cao

Kumar

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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It is a deeply engrained notion that the visual pigment rhodopsin signals light as a monomer, even though many G protein-coupled receptors are now known to exist and function as dimers. Nonetheless, recent studies (albeit all in vitro) have suggested that rhodopsin and its chromophore-free apoprotein, R-opsin, may indeed exist as a homodimer in rod disk membranes. Given the overwhelmingly strong historical context, the crucial remaining question, therefore, is whether pigment dimerization truly exists naturally and what function this dimerization may serve. We addressed this question in vivo with a unique mouse line (S-opsin + Lrat −/− ) expressing, transgenically, short-wavelength-sensitive cone opsin (S-opsin) in rods and also lacking chromophore to exploit the fact that cone opsins, but not R-opsin, require chromophore for proper folding and trafficking to the photoreceptor's outer segment. In R-opsin's absence, S-opsin in these transgenic rods without chromophore was mislocalized; in R-opsin's presence, however, S-opsin trafficked normally to the rod outer segment and produced functional S-pigment upon subsequent chromophore restoration. Introducing a competing R-opsin transmembrane helix H1 or helix H8 peptide, but not helix H4 or helix H5 peptide, into these transgenic rods caused mislocalization of R-opsin and S-opsin to the perinuclear endoplasmic reticulum. Importantly, a similar peptidecompetition effect was observed even in WT rods. Our work provides convincing evidence for visual pigment dimerization in vivo under physiological conditions and for its role in pigment maturation and targeting. Our work raises new questions regarding a potential mechanistic role of dimerization in rhodopsin signaling.rhodopsin | cone opsin | dimerization | protein trafficking R hodopsin and cone pigments mediate scotopic and photopic vision, respectively. They consist of opsin, the apo-protein, and 11-cis-retinal, a vitamin A-based chromophore. Light absorption by 11-cis-retinal triggers a conformational change in opsin, which in turn initiates a G protein-coupled receptor (GPCR) signaling pathway to lead to vision. Indeed, rhodopsin signaling is a prominent prototypical GPCR pathway from which a huge quantity of mechanistic details about such signaling in general has emerged. All along, it is a dogma that rhodopsin exists and functions as a monomer (1-6). About a decade ago, evidence began to emerge that rhodopsin may exist as a dimer, based on atomic force microscopy and cross-linking experiments performed on rod outersegment (ROS) disk membranes (7-9). However, this concept remains highly controversial because of the lack of in vivo evidence and also is puzzling because, unlike many GPCRs, monomeric rhodopsin is fully functional with respect to coupling to G protein (2, 4-6, 10) and to interactions with rhodopsin kinase and arrestin (11,12). In vivo evidence, albeit of paramount importance, is also challenging, because rhodopsin always exists as a single isoform in rod photoreceptors, thus making homomeric, higher-or...

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Cone outer segment extracellular matrix as binding domain for interphotoreceptor retinoid‐binding protein

Garlipp

Nowak

Gonzalez‐Fernandez

2012

J of Comparative Neurology

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Cones are critically dependent on interphotoreceptor retinoid-binding protein (IRBP) for retinoid delivery in the visual cycle. Cone-dominant vertebrates offer an opportunity to uncover the molecular basis of IRBP's role in this process. Here, we explore the association of IRBP with the interphotoreceptor matrix (IPM) of cones vs. rods in cone dominant retinas from chicken (Gallus domesticus), turkey (Meleagris gallopavo), and pig (Sus scrofa). Retinas were detached and fixed directly or washed in saline prior to fixation. Disassociated photoreceptors with adherent matrix were also prepared. Under 2 mM CaCl2, insoluble matrix was delaminated from saline washed retinas. The distribution of IRBP, as well as glycans binding peanut agglutinin (cone matrix) and wheat germ agglutinin (rod/cone matrix), was defined by confocal microscopy. Retina flat mounts showed IRBP diffusely distributed in an interconnecting, lattice-like pattern throughout the entire matrix. Saline wash replaced this pattern with fluorescent annuli surrounding individual cone outer segments. In isolated cones and matrix sheets, IRBP colocalized with the peanut agglutinin binding matrix glycans. Our results reveal a wash-resistant association of IRBP with a matrix domain immediately surrounding cone outer segments. The cone matrix sheath may be responsible for IRBP-mediated cone targeting of 11-cis retinoids.

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Breaking the Covalent Bond— A Pigment Property that Contributes to Desensitization in Cones

Cited by 98 publications

References 55 publications

Retinal Attachment Instability Is Diversified among Mammalian Melanopsins

Retinal Attachment Instability Is Diversified among Mammalian Melanopsins

Dimerization of visual pigments in vivo

Cone outer segment extracellular matrix as binding domain for interphotoreceptor retinoid‐binding protein

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