Molecular Mechanism of Cone Opsin Biosynthesis

University Of Connecticut Health Center, Farmington CT

Investigators

Abstract

Visual pigments are the proteins that capture light and convert light signal to neural signal in the photoreceptor cells in the retina. Red, green, and blue visual pigments absorb light at long, medium, and short wavelength, respectively, in cone photoreceptors and mediate day vision in humans. Throughout our lives, visual pigments are continuously synthesized and transported to the outer segments of photoreceptor cells. Removal and renewal of a substantial portion of the visual pigments take place every day. Daylight vision in all animals relies heavily on cone visual pigments; however, little is known about the biosynthetic process of cone visual pigments. Starting with the translation of the mRNA, the biosynthesis of visual pigments occurs in multiple stages. It involves insertion of the translated protein into the lipid bilayer, and co- and post-translational modifications that potentially include changes in the folding-intermediate structures. Subsequently, binding of 11-cis retinal and formation of the light sensitive pigment, and transport to the final destination in the outer segment occur. Our previous studies showed that the folding of red-cone pigment to the functional three-dimensional structure requires help from another protein called Ran binding protein 2 (RanBP2), a large multi-functional protein. The goal of this project is to determine when RanBP2 is required during the red opsin biosynthetic pathway and what specific role(s) it subserves. Red opsin will be produced in the presence and absence of various domains of RanBP2 in mammalian cells. How the synthesis, folding, stability, or degradation of red opsin are affected by different domains of RanBP2 will be investigated. Results from this study will provide insight into the molecular mechanism of cone opsin biosynthesis for the first time.