GONZALEZ-FERNANDEZ, Federico: Evolution and Functions of Retinoid-binding Proteins “RBPs”: The interphotoreceptor “IRBP”

The design of the vertebrate retina took a radical departure from that of invertebrates. The involution of the optic vesicle allows photoreceptors to be closely packed and the pigmented epithelium (RPE) and photoreceptors divide the labor of biochemical processes such as the visual cycle. Interactions between these two cell layers are mediated by the interphotoreceptor matrix (IPM). A gene not functioning in vision was recruited to create interphotoreceptor retinoid-binding protein (IRBP) the major soluble protein component of the IPM. The primordial gene was quadruplicated to encode a single polypeptide consisting of four modules each 300 amino acids. IRBP is secreted by the photoreceptors into the IPM where its large size prevents it from escaping from the subretinal space. Although trapped, IRBP is rapidly turned over. IRBP may promote the exchange of 11-cis retinal and all-trans retinol by facilitating their diffusion, targeting the delivery of all-trans retinol to the RPE, promoting the release of 1l-cis retinal from the RPE, and protecting these retinoids from degradation. Transgenic mice lacking IRBP show no reduction in the rate of retinoid transport, but do undergo photoreceptor degeneration. X-ray structure of one of the modules identifies two domains separated by a hydrophobic ligand-binding domain. A structural homology to the recently solved photosystem II D1 C-terminal processing protease and the enoyl-CoA isomerase/hydratase family suggests the utility of a common fold used in diverse settings ranging from proteolysis, to fatty acid isomerization to retinoid transport. In summary, IRBP is important to the integrity of the retina however its precise function is not clearly established. As experimentation proceeds an open mind to old and new avenues of research is needed.