Disease relevance of ninaE

• The Drosophila Rh1 rhodopsin gene was the first gene shown to cause retinal degeneration when mutated [1].
• Rhodopsin formation in Drosophila is dependent on the PINTA retinoid-binding protein [2].
• Some of these dominant rod opsin mutant proteins, which desensitize transgenic Xenopus rods, provide an animal model for congenital night blindness [3].
• Expression of the E. coli genes was then used to assay the ability of various sequences from the ninaE gene to confer the ninaE pattern of expression [4].
• rhodopsin mutations result in autosomal dominant retinitis pigmentosa (ADRP), the most frequent being Proline-23 substitution by histidine (RhoP23H) [5].

High impact information on ninaE

• Homothorax increases rhabdomere size and uncouples R7-R8 communication to allow both cells to express the same opsin rather than different ones as required for color vision [6].
• 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 [7].
• 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 [7].
• The theory quantitatively describes the inactivation kinetics of activated rhodopsin in vivo and can be independently tested with molecular and spectroscopic data [8].
• We now show that mutations in the ninaA gene severely inhibit opsin transport from the ER, leading to dramatic accumulations of ER cisternae in the photoreceptor cells [9].

Chemical compound and disease context of ninaE

• 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 [2].
• Growth of a variety of human cell lines (rhabdomyosarcoma cell lines Rh1, Rh18, Rh28 and Rh30; MCF-7, KB-3-1 and their adriamycin-resistant counterparts; National Cancer Institute 60 human tumor cell lines comprising nine tumor types) is inhibited by olomoucine [10].

Biological context of ninaE

• 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 [11].
• This opsin gene contains no introns and encodes a 383 amino acid polypeptide that is approximately 35% homologous to the blue absorbing ninaE and Rh2 opsins, which are expressed in photoreceptor cells R1-6 and R8, respectively [12].
• 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) [13].
• 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 [9].
• Arrestin1 mediates light-dependent rhodopsin endocytosis and cell survival [14].

Anatomical context of ninaE

• Null mutations of the Drosophila Rh1 rhodopsin gene, ninaE, result in developmental defects in the photosensitive membranes, the rhabdomeres, of compound eye photoreceptors R1-R6 [15].
• In ninaE null mutants, these catacombs do not form and developing rhabdomere membrane involutes into the cell as curtains of apposed plasma membrane [15].
• Intriguingly, we have found a third isoform, dgqC, which is specifically and abundantly expressed in male gonads, and shares the divergent rhodopsin-binding exon of dgqA [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].
• It is hypothesized that (1) this accumulation of membranes may be caused by the failure of newly synthesized membranes that are inserted into the base of microvilli to be assembled into R1-6 rhabdomeres and (2) this failure may be caused by the extremely low concentration of normal R1-6 rhodopsin in the ninaE mutants [18].

Associations of ninaE with chemical compounds

• Freeze fracture reveals that delta Asn20's rhabdomeric P-face particle count is as low as for vitamin A deprivation, consistent with an opsin defect [19].
• Receptor demise from alteration of glycosylation site in Drosophila opsin: electrophysiology, microspectrophotometry, and electron microscopy [19].
• We placed UAA, UAG and UGA nonsense mutations at two leucine codons, Leu205 and Leu309, in Drosophila's major rhodopsin gene, ninaE, by site-directed mutagenesis, and then created the corresponding mutants by P element-mediated transformation of a ninaE deficiency strain [20].
• Here we report that transgenic expression of a dominant-active Drosophila Rho guanosine triphosphatase, Drac1, rescued photoreceptor morphogenesis in rhodopsin-null mutants; expression of dominant-negative Drac1 resulted in a phenotype similar to that seen in rhodopsin-null mutants [21].
• Opsin expression is extremely suppressed by carotenoid deprivation in Drosophila [22].

Physical interactions of ninaE

• These results establish a role for Rab11 in the post-Golgi transport of rhodopsin and of other proteins to the rhabdomeric membranes of photoreceptors, and in analogous transport processes in other cells [23].

Co-localisations of ninaE

• One hour after release from the endoplasmic reticulum, rhodopsin colocalizes with Rab11 in vesicles at the base of the rhabdomere [23].

Regulatory relationships of ninaE

• These results suggest that Pax-6/Ey directly regulates rhodopsin 1 gene expression by binding to the conserved P3/RCS1 element in the promoter [24].

Other interactions of ninaE

• We found that, in contrast, opsin Rh2 is the predominant opsin expressed in the ocelli [25].
• Moreover, a detailed noise analysis shows that photoreceptor responses of both a ninaE mutant and a ninaD mutant follow the adapting bump model [26].
• Numerous changes have occurred in these genes since the duplications, including the loss and/or gain of introns in the different genes and even within the Rh1 and Rh4 clades [27].
• In addition, we show that two mutants that specifically affect the R1-R6 cells, ninaA and rdgB, do not directly affect expression of the ninaE gene [11].
• RESULTS: We show, for the first time, that visual pigment appears pink in white light, especially for Rh1 and Rh6 [28].

Analytical, diagnostic and therapeutic context of ninaE

• We have used in situ hybridization to study the messenger RNAs expressed by these four opsin genes in all three visual organs [25].
• Novel Gq alpha isoform is a candidate transducer of rhodopsin signaling in a Drosophila testes-autonomous pacemaker [16].
• The sequence alignment of Lo1 reveals significant homology to mantid opsin [29].
• Recovery of Rh1 protein upon such carotenoid replacement followed, barely detectable on Western blots at 4 hr but conspicuous by 8 hr [30].
• Northern blots on Drosophila heads showed that mRNA of Rh1 (the predominant rhodopsin) was high in vitamin A replete controls, very low in deprived flies, and increased upon feeding carrot juice to deprived flies as early as 1 hr [30].

References