Fourth module of Xenopus interphotoreceptor retinoid-binding protein: activity in retinoid transfer between the retinal pigment epithelium and rod photoreceptors

Gonzalez‐Fernandez, Federico; Baer, Claxton; Baker, Evelyn; Okajima, Ting Ing L; Wiggert, Barbara; Braiman, Mark S.; Pepperberg, David R.

doi:10.1076/ceyr.17.12.1150.5129

Cited by 13 publications

(7 citation statements)

References 32 publications

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“…Although the IRBP and serum albumin proteins that we have used are from bovine, the mammalian and amphibian IRBPs are homologous (58,59). This is particularly relevant in considering the implications of the results for the physiological concentrations of the carriers.…”

Section: Discussionmentioning

confidence: 99%

Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Blakeley

Cornwall

et al. 2007

Biochemistry

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Light detection by vertebrate rod photoreceptor outer segments results in the destruction of the visual pigment, rhodopsin, as its retinyl moiety is photoisomerized from 11-cis to all-trans. The regeneration of rhodopsin is necessary for vision and begins with the release of the all-trans retinal and its reduction to all-trans retinol. Retinol is then transported out of the rod outer segment for further processing. We used fluorescence imaging to monitor retinol fluorescence and quantify the kinetics of its formation and clearance after rhodopsin bleaching in the outer segments of living isolated frog (Rana pipiens) rod photoreceptors. We independently measured the release of all-trans retinal from bleached rhodopsin in frog rod outer segment membranes and the rate of all-trans retinol removal by the lipophilic carriers interphotoreceptor retinoid binding protein (IRBP) and serum albumin. We find that the kinetics of all-trans retinol formation in frog rod outer segments after rhodopsin bleaching are to a good first approximation determined by the kinetics of all-trans retinal release from the bleached pigment. For the physiological concentrations of carriers, the rate of retinol removal from the outer segment is determined by the IRBP concentration, while the effect of serum albumin is negligible. The results indicate the presence of a specific interaction between IRBP and rod outer segment, probably mediated by a receptor. The effect of different concentrations of IRBP on the rate of retinol removal shows no cooperativity and has an EC 50 of 40 μmol/L.The vertebrate cells responsible for vision are the rod and cone photoreceptors of the retina that convert incoming light to an electrical signal. This conversion takes place in the photoreceptor outer segments, which are full of membrane disks containing the visual pigment, and, in a physiologically important arrangement, are enveloped by the retinal pigment epithelium (RPE). The visual pigment is composed of a chromophore, 11-cis retinal, attached to an integral membrane protein, opsin. The detection of light begins with the absorption of incoming photons by the visual pigment. An absorbed photon isomerizes the chromophore † Supported by NIH/NEI grants EY14850 (YK), EY04939 (RKC) , NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript moiety from 11-cis to all-trans bringing about a conformational change that initiates a cascade of reactions culminating in membrane potential change. The recovery of the cell from light involves the deactivation of the intermediates activated by light, and the reestablishment of membrane potential (1,2). However, the isomerized chromophore, all-trans retinal, remains. For vision to be possible, it is essential that the visual pigment regenerate: that is, the alltrans retinal has to be removed, and fresh 11-cis retinal has to be provided to combine with opsin and reform the visual pigment. The reactions regenerating the pigment are known as the Visual Cycle (3-5).In the case of the rod photoreceptors, t...

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Section: Discussionmentioning

confidence: 99%

Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Blakeley

Cornwall

et al. 2007

Biochemistry

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“…Each module contains roughly 300 amino acid residues distributed into two domains, A and B (Dettai and Lecointre, 2008). The individual modules appear to represent functional units of the protein (Baer et al, 1998a; Gonzalez-Fernandez et al, 1998; Gonzalez-Fernandez et al, 2007; Gross et al, 2000; Loew et al, 2001; Nickerson et al, 1998). X-ray crystallographic and site-directed mutagenesis studies of Xenopus apo IRBP-module 2 (x2) have identified a novel hydrophobic cavity within domain A (Gonzalez-Fernandez et al, 2009), and a hydrophobic cleft in domain B.…”

Section: Introductionmentioning

confidence: 99%

Structure of zebrafish IRBP reveals fatty acid binding

Ghosh

Haswell

Sprada

et al. 2015

Experimental Eye Research

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Interphotoreceptor retinoid-binding protein (IRBP) has a remarkable role in targeting and protecting all-trans and 11-cis retinol, and 11-cis retinal during the rod and cone visual cycles. Little is known about how the correct retinoid is efficiently delivered and removed from the correct cell at the required time. It has been proposed that different fatty composition at that the outer-segments and retinal-pigmented epithelium could have an important role is regulating the delivery and uptake of the visual cycle retinoids at the cell-interphotoreceptor-matrix interface. Although this suggests intriguing mechanisms for the role of local fatty acids in visual-cycle retinoid trafficking, nothing is known about the structural basis of IRBP-fatty acid interactions. Such regulation may be mediated through IRBP’s unusual repeating homologous modules, each containing about 300 amino acids. We have been investigating structure-function relationships of Zebrafish IRBP (zIRBP), which has only two tandem modules (z1 and z2), as a model for the more complex four-module mammalian IRBP’s. Here we report the first X-ray crystal structure of a teleost IRBP, and the only structure with a bound ligand. The X-ray structure of z1, determined at 1.90Å resolution, reveals a two-domain organization of the module (domains A and B). A deep hydrophobic pocket was identified within the N-terminal domain A. In fluorescence titrations assays, oleic acid displaced all-trans retinol from zIRBP. Our study, which provides the first structure of an IRBP with bound ligand, supports a potential role for fatty acids in regulating retinoid binding.

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“…To examine this possibility directly, we tested whether ath5 induced the expression of other photoreceptor-specific genes and whether the transdifferentiating cells, when provided a more adhesive substratum, would develop morphologies typical of photoreceptor cells. Characteristic photoreceptor-specific genes include IRBP, which plays an important role in recycling and/or regeneration of retinoid (Gonzalez-Fernandez et al, 1998); the gene encoding the red pigment, a hallmark of cones that sense red light; and rhodopsin, a hallmark of rods. Whereas IRBP expression begins early during photoreceptor differentiation, genes encoding photopigments are expressed during late phases of photoreceptor development (Bruhn and Cepko, 1996); thus, their expression would indicate that ath5 triggered the expression of genes associated with photoreceptor differentiation.…”

Section: Induction Of Rpe Transdifferentiation Toward Photoreceptor Cmentioning

confidence: 99%

A Role ofath5in InducingneuroDand the Photoreceptor Pathway

Yan²,

Xie³

et al. 2004

J. Neurosci.

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Photoreceptors in the vertebrate retina are light-sensitive neurons, and their degeneration results in irreversible visual loss. Understanding how photoreceptor fate is determined is a prerequisite for developing photoreceptor replacement therapies. Previous studies identified two basic helix-loop-helix genes, neurogenin2 (ngn2) and neuroD, participating in a genetic pathway leading to photoreceptor genesis. Here we present experimental data suggesting that ath5, which is known for its critical role in retinal ganglion cell development, may also lead to photoreceptor production. In the developing retina, ath5 expression was detected in two zones of cells, and coexpression with neuroD was observed in the zone adjacent to young photoreceptor cells accumulating on the retinal pigment epithelial side. Retroviral-driven misexpression of ath5 in retinal cells increased the population of photoreceptor cells, as well as ganglion cells, in a developmental stage-dependent manner that is consistent with ath5 being involved in the development of multiple types of retinal neurons. Ectopic ath5 expression in cultures of non-neural retinal pigment epithelial cells elicited transdifferentiation into cells that expressed photoreceptor-specific genes and displayed photoreceptor-like morphologies. Gene expression analysis showed that ngn2 did not induce ath5, and ath5 did not induce ngn2, but both induced neuroD and RaxL. These data suggest a pathway of "ath5 3 neuroD 3 photoreceptor genes" separate from yet convergent with the ngn2 pathway.

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Fourth module of Xenopus interphotoreceptor retinoid-binding protein: activity in retinoid transfer between the retinal pigment epithelium and rod photoreceptors

Abstract: The results indicate a low but significant activity of IRBP's fourth module in reactions relevant to retinoid exchange.

Cited by 13 publications

References 32 publications

Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Structure of zebrafish IRBP reveals fatty acid binding

A Role ofath5in InducingneuroDand the Photoreceptor Pathway

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