Disease relevance of Rh5

• These results establish that rhodopsin is transported via a Rab6 regulated pathway and that defects in trafficking pathways lead to retinal degeneration [1].
• rhodopsin mutations result in autosomal dominant retinitis pigmentosa (ADRP), the most frequent being Proline-23 substitution by histidine (RhoP23H) [2].
• Rhodopsin formation in Drosophila is dependent on the PINTA retinoid-binding protein [3].
• We propose that the sequestering of arrestin to membranes is a possible mechanism for retinal disease associated with previously identified rhodopsin alleles in humans [4].
• Interactions between TcTex-1 and a diverse set of proteins such as the dynein intermediate chain, Fyn, DOC2, FIP1, the poliovirus receptor, CD155, and the rhodopsin cytoplasmic tail have been reported; yet, despite the broad range of targets, a consensus binding sequence remains uncertain [5].

High impact information on Rh5

• 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 Rh5

• 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 [3].

Biological context of Rh5

• We have cloned three novel Calliphora rhodopsins, which are homologues of Drosophila Rh3, Rh5 and Rh6, with an amino acid sequence identity of 80.7%, 60.9% and 86.1%, respectively [10].
• We show here that the distinction between the rhodopsins expressed in the two classes of ommatidia depends on a series of highly conserved homeodomain binding sites present in the rhodopsin promoters [11].
• Rhodopsin mutations as the cause of retinal degeneration. Classification of degeneration phenotypes in the model system Drosophila melanogaster [12].
• Unlike the 49-kilodalton protein, however, arrestin, which appears to bind to phosphorylated rhodopsin, has not itself been reported to undergo phosphorylation [13].
• Coupling of photoexcited rhodopsin to inositol phospholipid hydrolysis in fly photoreceptors [14].

Anatomical context of Rh5

• A new rhodopsin in R8 photoreceptors of Drosophila: evidence for coordinate expression with Rh3 in R7 cells [15].
• The interaction of photoexcited rhodopsin with a G protein is thus similar in both vertebrate and invertebrate photoreceptors [14].
• In Drosophila, rhodopsin (Rh1), the most abundant rhodopsin, is glycosylated in the endoplasmic reticulum (ER) and requires its molecular chaperone, NinaA, for exit from the ER and transport through the secretory pathway [16].
• 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 [17].
• Drac1 was localized in a specialization of the photoreceptor cortical actin cytoskeleton, which was lost in rhodopsin-null mutants [18].

Associations of Rh5 with chemical compounds

• 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 [19].
• 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 [1].
• 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) [16].
• Role of asparagine-linked oligosaccharides in rhodopsin maturation and association with its molecular chaperone, NinaA [16].
• Unlike the previously characterised insect visual pigments which have 3-hydroxy retinal in their binding sites, mantid rhodopsin contains 11-cis retinal [20].

Other interactions of Rh5

• Rh3 and Rh5 are present in most cases in the same ommatidia, which account for approximately 27% of all ommatidia, and Rh6 is found in the complementary 73% [10].
• Here, we describe the identification of a new opsin gene, rhodopsin 5, expressed in one subclass of R8 cells [15].

Analytical, diagnostic and therapeutic context of Rh5

• Microspectrophotometry was used to compare the rhodopsin concentrations in wild-type flies and norpA vision transduction mutants [21].
• Novel Gq alpha isoform is a candidate transducer of rhodopsin signaling in a Drosophila testes-autonomous pacemaker [22].
• Proteins were resolved by polyacrylamide gel electrophoresis (PAGE) and subjected to immunoblot analysis using antibodies directed to rhodopsin, NinaA, Arr1, and Arr2 [23].
• 1 microm frozen sections were cut on an ultracryomicrotome, then stained with antibodies specific for rhodopsin or arrestin [24].

References