Disease relevance of rdgA

• Furthermore, we show that light, Gq and PLCbeta all modulate retinal degeneration in rdgA [1].

High impact information on rdgA

• Together our results demonstrate the contribution of PI depletion to the rdgA phenotype and provide evidence that depletion of PI and its metabolites might be a key signal for TRP channel activation in vivo [2].
• We demonstrate that the synergistic activity of laza and rdgA regulates response termination during phototransduction [2].
• We now find that quantum bumps in such mutants are reduced approximately 3- to 5-fold but are restored to near wild-type values by mutations in the rdgA gene encoding diacylglycerol kinase (DGK) and also by depleting intracellular ATP [3].
• The findings suggest that early degeneration in rdgA is caused by uncontrolled Ca2+ influx and support the proposal that diacylglycerol or its metabolites are messengers of excitation in Drosophila photoreceptors [4].
• This gene, designated as DGK2, has a single open reading frame that encodes 1454 amino acids [5].

Chemical compound and disease context of rdgA

• The analysis of the eyes of mutants homozygous for rdgA and eye-protein kinase C mutations indicates that retinal degeneration is caused by the deficiency of PA rather than excessive accumulation of DG [6].

Biological context of rdgA

• In this study, using a novel forward-genetic screen, we identified InaD, a multivalent PDZ domain protein as a suppresser of retinal degeneration in rdgA mutants [1].
• To examine whether rdgA gene dosage effect holds for other enzymes related to the phosphatidylinositol turnover, phospholipase C was analyzed which did not show any gene dosage effect [7].
• In this study, we show that retinal degeneration is prevented by the introduction of the eye-DGK gene in the rdgA mutant genome, suggesting that the DGK activity is crucial for the maintenance of the photoreceptor [6].
• Furthermore, in two rdgA alleles, rdgA1 and rdgA2, nonsense and missense mutations occur within their DGK2 gene, respectively [5].

Anatomical context of rdgA

• These results suggest that the process of turnover of rhabdomeric microvilli is abnormal in rdgA [8].
• Incorporations of 3H-amino acids, and 3H-mannose and 3H-glucosamine residues into the photoreceptive membranes were studied in newly emerged rdgA mutant flies by electron microscope autoradiography [9].
• The DGK2 protein contains four ankyrin-like repeats at the C-terminal region, suggesting that DGK2 is likely anchored to the membrane or cytoskeleton [5].

Associations of rdgA with chemical compounds

• Whole-cell recordings revealed that light-sensitive Ca2+ channels encoded by the trp gene were constitutively active in rdgA photoreceptors [4].
• Furthermore, by immunohistochemical analysis, we have demonstrated that the rdgA protein is predominantly associated with the SRC, suggesting that the conversion from diacylglycerol (DG) to phosphatidic acid (PA) most actively occurs in SRC [6].

Other interactions of rdgA

• Rescue of light responses in the Drosophila "null" phospholipase C mutant, norpAP24, by the diacylglycerol kinase mutant, rdgA, and by metabolic inhibition [10].
• The most compelling evidence for this view comes from analysis of rdgA mutants which are unable to effectively metabolise DAG due to a defect in DAG kinase [11].
• Functional INAD complexes are required to mediate degeneration in photoreceptors of the Drosophila rdgA mutant [1].
• The defects in the rdgA and rdgB mutants were localized by the study of genetic mosaics to the photoreceptor cells [12].

Analytical, diagnostic and therapeutic context of rdgA

• We report the molecular cloning and characterization of a DGK gene, which maps to the rdgA locus [5].
• Northern blot analysis and tissue in situ hybridization to adult sections revealed that DGK2 is expressed exclusively in the adult retina and that the amount of its mRNA is reduced in some of the rdgA mutant alleles [5].
• Analysis of photoreceptor membrane turnover in a Drosophila visual mutant, rdgA, by electron microscope autoradiography [9].

References