Disease relevance of Pdc

• These data thus confirm and extend the findings of previous work that local trophic interactions are important in regulating rod photoreceptor degeneration in retinitis pigmentosa [1].
• Immunization with PDC(R)65-96 (amino acid residues 65 through 96 derived from rat phosducin) at doses of 0.83 nmol or more induced severe experimental autoimmune uveitis (EAU) in all rats within 12 days [2].
• Viral vectors based on the nonpathogenic human adeno-associated virus, when coupled with the strong, rod photoreceptor specific opsin promoter, offer an efficient and nontoxic way to deliver and express ribozymes in photoreceptor cells for long time periods of time [3].
• Low dark-adapted, scotopic retinal and visual sensitivity in retinopathy of prematurity (ROP) could be due to disease of the inner retina, or the recently described rod photoreceptor abnormalities [4].

High impact information on Pdc

• A key component in dark/light adaptation is phosducin, a phosphorylatable protein that modulates the amount of transducin heterotrimer (Gt alpha beta gamma) available through sequestration of the beta gamma subunits (Gt beta gamma) [5].
• Rod photoreceptor development in vitro: intrinsic properties of proliferating neuroepithelial cells change as development proceeds in the rat retina [6].
• Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes [7].
• An isoform of the rod photoreceptor cyclic nucleotide-gated channel beta subunit expressed in olfactory neurons [8].
• CNG4.3 derives from the same gene as the rod photoreceptor beta subunit (CNG4.1) but lacks the long, glutamic acid-rich domain found in the N terminus of CNG4 [8].

Biological context of Pdc

• Rat phosducin also contains three potential phosphorylation domains for protein kinase C and nine for casein kinase II as well as a predicted site for N-glycosylation [9].
• The product of one of these genes has extensive sequence homology to phosducin, a phosphoprotein expressed in retina and pineal gland that modulates trimeric guanine nucleotide-binding protein (G protein) function by binding to G-protein beta gamma subunits [10].
• The IC50 value of PhLP in the latter assay was 89 nM, whereas phosducin caused half-maximal inhibition at 17 nM [11].
• We identified from a rat brain cDNA library an isolate encoding the phosducin-like protein (PhLP), which has 41% identity and 65% amino acid homology to phosducin [10].
• By manipulating cell density in serum-free cultures we show that rat rod photoreceptor development requires a diffusible activity produced by neonatal retinal cells [12].

Anatomical context of Pdc

• In pursuit of the function of phosducin, we tested the hypothesis that it regulates the light-driven translocation of G protein transducin from the outer segments of rod photoreceptors to other compartments of the rod cell [13].
• Phosducin is a cytosolic protein predominantly expressed in the retina and the pineal gland that can interact with the betagamma subunits of guanine nucleotide binding proteins (G proteins) and thereby may regulate transmembrane signaling [11].
• PCR amplification detected the expression of transcripts for subunit 1 of both the rod photoreceptor (RCNGC1) and the olfactory receptor cell (OCNGC1) subtype of CNG channel in adult rat hippocampus [14].
• Recent evidence indicates that 9-cis retinoic acid, which acts through members of the steroid/thyroid superfamily of receptors, directs progenitor cells to the rod photoreceptor cell fate [15].
• RESULTS: At the onset of rod photoreceptor birth (E14), laminin beta 2 surrounds the cells of the retinal pigmented epithelium (RPE) and is present on the apical surface of the retinal neuroepithelium [16].

Associations of Pdc with chemical compounds

• These results provide evidence for three activities, one of which is taurine, that are candidate regulators of rod photoreceptor development in vivo [17].
• The purified receptor was then reconstituted into lipid vesicles, and its ability to activate either transducin, the rod photoreceptor-specific GTP-binding protein, or the alpha subunit of Go was assayed in vitro using a guanosine 5'-3-O-(thio)triphosphate binding assay [18].
• In addition, total (dephosphorylated) MEKA was observed to increase after a 6-h treatment with norepinephrine or (Bu)2 cAMP, an effect which was dependent upon new protein synthesis [19].
• Retinoic acid promotes rod photoreceptor differentiation in rat retina in vivo [20].
• In contrast, the low insulin dose which reduced serum glucose approximately 30% elicited a significant adrenocortical response only in the intact or PHD groups but failed to stimulate this response in animals with CHD or AHD [21].

Regulatory relationships of Pdc

• Ciliary neurotrophic factor blocks rod photoreceptor differentiation from postmitotic precursor cells in vitro [22].

Other interactions of Pdc

• Our study identifies a proliferative intermediate precursor, characterized by Mash1 expression, that is the target of EGF-mediated suppression of rod photoreceptor differentiation [23].
• Role of the isoprenyl pocket of the G protein beta gamma subunit complex in the binding of phosducin and phosducin-like protein [24].
• Rats carrying transgenes with P23H and S334ter rhodopsin mutations lose their photoreceptors and have lower levels of 22:6n-3 in rod photoreceptor outer segments (ROS) than wild type (WT) animals [25].
• However, coexpression of both phosducin and beta-arrestin 1 reverses this blockade [26].
• The effect of age on the endogenous production of reactive oxygen species, catalase activity and lipid peroxidation in isolated rod photoreceptor outer segment membranes of Long-Evans rat retina was investigated [27].

Analytical, diagnostic and therapeutic context of Pdc

• Gating by cGMP and voltage of the alpha subunit of the cGMP-gated channel from rod photoreceptor was examined with a patch-clamp technique [28].
• It was confirmed that MEKA is rapidly phosphorylated by adrenergic stimulation of pineal glands in organ culture [19].
• In this report, the subcellular distribution and amounts of rat Pd are quantified with immunogold electron microscopy [29].
• Both stainings revealed immunoreactivity in Müller cells and particularly in their processes tightly ensheathing rod photoreceptor terminals [30].
• METHODS: Antigen peptides were synthesized according to the amino acid sequence of the rat-derived phosducin with a peptide-synthesizer and purified by reversed-phase HPLC [31].

References