Disease relevance of Rh2

• Expression of the E. coli genes was then used to assay the ability of various sequences from the Rh2 gene to confer upon the indicator genes the Rh2 pattern of expression [1].
• rhodopsin mutations result in autosomal dominant retinitis pigmentosa (ADRP), the most frequent being Proline-23 substitution by histidine (RhoP23H) [2].
• We further show that Rh1(N20I) interferes with wild type Rh1 maturation and triggers a dominant form of retinal degeneration [3].
• Rhodopsin formation in Drosophila is dependent on the PINTA retinoid-binding protein [4].
• We propose that the sequestering of arrestin to membranes is a possible mechanism for retinal disease associated with previously identified rhodopsin alleles in humans [5].

High impact information on Rh2

• The Rhesus blood-group antigens are defined by a complex association of membrane polypeptides that includes the non-glycosylated Rh proteins (RhD and RhCE) and the RHag glycoprotein, which is strictly required for cell surface expression of these antigens [6].
• Despite their importance in transfusion medicine, the function of RhAG and Rh proteins remains unknown, except that their absence in Rh(null) individuals leads to morphological and functional abnormalities of erythrocytes, known as the Rh-deficiency syndrome [6].
• The theory quantitatively describes the inactivation kinetics of activated rhodopsin in vivo and can be independently tested with molecular and spectroscopic data [7].
• In Drosophila, the major rhodopsin Rh1 is synthesized in endoplasmic reticulum (ER)-bound ribosomes of the R1-R6 photoreceptor cells and is then transported to the rhabdomeres where it functions in phototransduction [8].
• We have used P-element-mediated transformation to introduce the cloned Rh1 rhodopsin gene into the germ line of Drosophila and fully rescue the visual phenotype of mutant ninaE flies [9].

Chemical compound and disease context of Rh2

• In a genetic screen for mutations that affect the biosynthesis of rhodopsin, we identified a novel CRAL-TRIO domain protein, prolonged depolarization afterpotential is not apparent (PINTA), which binds to all-trans-retinol [4].

Biological context of Rh2

• The ocellar-specific gene expression of Rh2 is of particular interest for its possible bearing on the function of the ocellus [10].
• We have determined the DNA sequence of the Rh2 promoter from -448 to +32 and have found an 11-bp sequence which is also present in the upstream flanking sequences of two other photoreceptor-specific genes (ninaE and ninaC) [1].
• By screening retinal cDNA libraries for photoreceptor-specifically expressed genes we have isolated and sequenced a cDNA clone encoding the rhodopsin (Rh6) of a subset of R8 photoreceptor cells of the Drosophila compound eye [11].
• By driving either ninaE(D1) or ninaE+ expression from a heat-shock promoter, we show that the 80-kD rhodopsin complex forms immediately after gene activation [12].
• Rh1 rhodopsin localizes to and is essential for the development and maintenance of the rhabdomere, the specialized membrane-rich organelle that serves as the site of phototransduction [13].

Anatomical context of Rh2

• Since R8 cells are founder cells in the developing compound eye, the isolation of a rhodopsin gene expressed in these cells may aid the understanding of terminal differentiation of photoreceptor cells [11].
• This proposal is supported by the finding that rhodopsin 2 and arrestin 1, two photoreceptor-cell-specific genes, are also expressed in male gonads [14].
• First, we show the dual-localization of mutant Rhodopsin since most of Rh1P37H accumulates in endoplasmic reticulum [2].
• Drac1 was localized in a specialization of the photoreceptor cortical actin cytoskeleton, which was lost in rhodopsin-null mutants [15].
• Translocation of three signaling molecules is covered in this review: (1) Light-dependent translocation of arrestin from the cytosol to the signaling membrane, the rhabdomere, determines the lifetime of activated rhodopsin [16].

Associations of Rh2 with chemical compounds

• The generation of monomeric forms of wild-type rhodopsin is suppressed in vitamin A-deprived flies or in flies heterozygous for the dominant rhodopsin mutation [12].
• Chimeric Rh1 pigments carrying individual substitutions of the cytoplasmic loops C2 and C3 and the C-terminus with the corresponding regions of Rho retained the ability to stimulate phototranduction in Drosophila, but failed to activate transducin [17].
• We investigated the role of Rh1 glycosylation and Rh1/NinaA interactions under in vivo conditions by analyzing transgenic flies expressing Rh1 with isoleucine substitutions at each of the two consensus sites for N-linked glycosylation (N20I and N196I) [3].
• Role of asparagine-linked oligosaccharides in rhodopsin maturation and association with its molecular chaperone, NinaA [3].
• We overexpressed wild-type, a GTPase defective (Q71L), and a guanine nucleotide binding defective (N125I) Rab6 protein in Drosophila photoreceptors to assess the in vivo role of Rab6 in the trafficking of rhodopsin and other proteins [18].

Other interactions of Rh2

• We found that, in contrast, opsin Rh2 is the predominant opsin expressed in the ocelli [10].
• We found that Rh3 and Rh4 are as well, but not Rh2 [10].

Analytical, diagnostic and therapeutic context of Rh2

• Proteins were resolved by polyacrylamide gel electrophoresis (PAGE) and subjected to immunoblot analysis using antibodies directed to rhodopsin, NinaA, Arr1, and Arr2 [19].
• Novel Gq alpha isoform is a candidate transducer of rhodopsin signaling in a Drosophila testes-autonomous pacemaker [14].
• 1 microm frozen sections were cut on an ultracryomicrotome, then stained with antibodies specific for rhodopsin or arrestin [20].

References