Evolution of the visual cycle: the role of retinoid-binding proteins

Abstract

The trafficking of retinoids in the retina represents a model to study soluble hormone-binding proteins in a complex system subject to profound evolutionary adaptations. Although a remarkable illustration of convergent evolution, all visual systems detect light in the same way, that is through the photoisomerization of an 11-cis retinoid to a corresponding trans isomer. What is strikingly different between the systems, is the mechanism by which the 11-cis chromophore is reformed and visual pigment regenerated in a process known as the visual cycle. The variations of the cycle address a problem inherent to retinoids themselves. That is, the properties that make these molecules suited for light detection also account for their susceptibility to oxidative and isomeric degradation, and cellular toxicity. The cycle therefore provides an opportunity to examine the role of soluble hormonebinding proteins within an integrative and evolutionary context. The present review focuses on interphotoreceptor retinoid-binding protein (IRBP), a controversial glycolipoprotein that recruits a protein fold common to Cterminal-processing proteases and the crotonase family. This unorthodox retinoid-binding protein is entrapped in the subretinal compartment of those eyes that translocate visual cycle retinoids between the photoreceptors and the retinal pigment epithelium. Recent studies suggest that we should look beyond a strictly carrier function if we are to appreciate the role of IRBP in the visual cycle. Here we draw lessons from other soluble hormone-binding proteins to anticipate avenues of future research likely to provide insight into the structure and function of IRBP in vision.

Biochemical Properties of Purified Human Retinol Dehydrogenase 12 (RDH12): Catalytic Efficiency toward Retinoids and C9 Aldehydes and Effects of Cellular Retinol-Binding Protein Type I (CRBPI) and Cellular Retinaldehyde-Binding Protein (CRALBP) on the Oxidation and Reduction of Retinoids

“…Photoreceptors lack either CRBPI (51) or CRALBP (52,53). Although RDH12 is highly active toward 11-cis-retinoids and CRALBP cannot interfere with its activity in photoreceptors, it is unlikely that RDH12 is involved in the metabolism of 11-cis-retinoids, because according to the current model of the visual cycle, 11-cis-retinol is produced and oxidized in the retinal pigment epithelium (RPE) (reviewed in ref 54) and 11-cis-retinal that diffuses into photoreceptors from RPE is likely to be sequestered by opsin in the outer segments of photoreceptors before it can reach RDH12. The most obvious retinoid substrate for RDH12 in photoreceptors is all-transretinaldehyde, which forms in large quantities by the photoisomerization of 11-cis-retinaldehyde.…”

Rhodopsin Formation inDrosophilaIs Dependent on the PINTA Retinoid-Binding Protein

“…Multiple RBPs have been described in mammals (for review, see Noy, 2000;Gonzalez-Fernandez, 2002). These include CRBPI, which also binds preferentially to all-trans-retinol (MacDonald and Ong, 1987;Levin et al, 1988).…”

“…In addition, some RBPs are thought to promote transfer of retinoids between cell types, whereas others are proposed to sequester retinoids to create concentration gradients that facilitate reactions that would otherwise be unfavorable (Noy, 2000;Gonzalez-Fernandez, 2002). However, the specific roles of many RBPs are unresolved.…”

Evolution and the origin of the visual retinoid cycle in vertebrates

“…We have not been able to identify IRBP homologues in the amphioxus and Ciona genomes. IRBP consists of four consecutive modules, each approximately 300 amino acid residues in size (Gonzalez-Fernandez 2002). The gene appears to have arisen from the quadruplication of an ancestral gene present in an early common ancestor of vertebrates (Nickerson et al 2006).…”

“…In teleosts, the IRBP gene has been further duplicated into two genes, each of which shows distinct structural features and expression patterns (Nickerson et al 2006). The three-dimensional structure of an individual module of IRBP suggested a probable homology between IRBP and two diverse protein families, the C-terminal transferase (CPTase) and the crotenase families (Gonzalez-Fernandez 2002). The early vertebrate ancestor might have recruited a CPTase/crotenase family protein for a new purpose, retinoid transport between photoreceptor cells and their neighbour cells, having facilitated the establishment of the vertebrate-type visual cycle.…”