Light/Dark Translocation of Alphatransducin in Mouse Photoreceptor Cells Expressing G90D Mutant Opsin

Abstract

Genomic analysis, from patients with retinal diseases such as retinitis pigmentosa (RP) and congenital night blindness (CNB), has provided convincing evidence that various subtypes of retinal diseases can result from mutations in the gene encoding rod opsin, a protein that binds 11-cis retinal to form the visual pigment, rhodopsin. Over 100 different mutations in this gene have been documented, and shown to co-segregate with autosomal dominant RP (Berson et al., 2002; Farrar et al., 2002; Nour and Naash, 2003) as well as a few other mutations with CNB (Dryja et al., 1993; Sieving et al., 1995; al Jandal et al., 1999). Interestingly when these CNB causing mutations are expressed in COS cells, they constitutively activated transducin in the dark while in the absence of 11-cis retinal (Dryja et al., 1993; Rao et al., 1994; Gross et al., 2003a; Gross et al., 2003b). Thus, the in vitro data suggests that the CNB mutations generate a persistent ‘dark light’ that saturates the rod photocurrent and severely depresses rod sensitivity in a manner similar to that produced by light. One of these CNB mutations resulted from the replacement of glycine at position 90 by aspartic acid (G90D), which has been shown to associate with an unusual trait of congenital stationary night blindness (CSNB) (Sieving et al., 1995).