Retinal Degeneration Slow (RDS) Glycosylation Plays a Role in Cone Function and the Regulation of RDS/ROM-1 Complex Formation [Cell Biology]
September 29th, 2015 by Stuck, M. W., Conley, S. M., Naash, M. I.
The photoreceptor-specific glycoprotein retinal degeneration slow (RDS, also called PRPH2) is necessary for the formation of rod and cone outer segments. Mutations in RDS cause rod and cone dominant retinal disease, and it is well established that both cell types have different requirements for RDS. However, the molecular mechanisms for this difference remain unclear. Although RDS glycosylation is highly conserved, previous study revealed no apparent function for the glycan in rods. In light of the highly conserved nature of RDS glycosylation we hypothesized that it is important for RDS function in cones, and could underlie part of the differential requirement for RDS in the two photoreceptor subtypes. We generated a knockin mouse expressing RDS without the N-glycosylation site (N229S). Normal levels of RDS and the unglycosylated RDS binding partner rod outer segment membrane protein-1 (ROM-1) were found in N229S retinas however cone electroretinogram responses were decreased by 40% at 6 months of age. Since cones make up only 3-5% of photoreceptors in the wild-type background, N229S mice were crossed into the nrl-/- background (in which all rods are converted to cone-like cells) for biochemical analysis. In N229S/nrl-/- retinas, RDS and ROM-1 levels were decreased by ~60% each. These data suggest that glycosylation of RDS is required for RDS function or stability in cones, a difference that may be due to extracellular vs. intradiscal localization of the RDS glycan in cones vs. rods.