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Gene Review

Pdc  -  phosducin

Mus musculus

Synonyms: 33 kDa phototransducing protein, PHD, Phosducin, RPR-1, Rod photoreceptor 1, ...
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Disease relevance of Pdc


High impact information on Pdc


Chemical compound and disease context of Pdc

  • In this study we have examined the consequences of activating the PHD oxygen-sensing pathway in cultured neonatal myocytes using ethyl-3,4 dihydroxybenzoate and dimethyloxalylglycine, inhibitors that, similar to hypoxia, inhibit this family of O2-dependent PHD enzymes [11].
  • Since alterations in glutamate metabolism have been described in different models of retinitis pigmentosa, we investigated in the present work whether changes in glutamate turnover occur in the degenerating rd1 retina and whether glutamate-mediated excitotoxic mechanisms may contribute to rod photoreceptor death in this model [12].

Biological context of Pdc


Anatomical context of Pdc


Associations of Pdc with chemical compounds

  • A 1217-nucleotide cDNA was isolated from a rat pineal library by DNA-DNA hybridization with a polymerase chain reaction-amplified cDNA of bovine retina mRNA for phosducin [14].
  • Degeneration is preceded by accumulation of cyclic GMP in the retina and is correlated with deficient activity of the rod photoreceptor cGMP-phosphodiesterase [10].
  • In the developing retina, inhibition of glycine receptor activity prevents proper rod photoreceptor development [18].
  • Recently an oxygen-sensing/transducing mechanism has been identified as a family of O2-dependent prolyl hydroxylase domain-containing enzymes (PHD) [11].
  • In normoxia, PHD hydroxylates a specific proline residue that directs the degradation of constitutively synthesized hypoxia-inducible factor-1alpha [11].
  • We found that in the dark-adapted rods, phosducin phosphorylated at serine 54 is compartmentalized predominantly in the ellipsoid and outer segment compartments [19].

Physical interactions of Pdc

  • First, we have demonstrated that transducin beta gamma subunits interact with phosducin along their entire intracellular translocation route, as evident from their co-precipitation in serial tangential sections from light-adapted but not dark-adapted retinas [15].
  • The gamma subunit of the rod photoreceptor cGMP phosphodiesterase can modulate the proteolysis of two cGMP binding cGMP-specific phosphodiesterases (PDE6 and PDE5) by caspase-3 [20].

Regulatory relationships of Pdc


Other interactions of Pdc

  • Second, we generated a phosducin knockout mouse and found that the degree of light-driven transducin translocation in the rods of these mice was significantly reduced as compared with that observed in the rods of wild type animals [15].
  • We expressed the gamma subunit of mouse rod photoreceptor cGMP phosphodiesterase (PDE) in the bacterial pGFX-2TK expression vector which produces a cleavable 40 kDa fusion protein [24].
  • Phosducin is found exclusively in photoreceptor cells, including the synaptic and nuclear layers, while phosducin-like protein is found throughout the inner retinal layers, most abundantly in the bipolar cells of the inner nuclear layer [25].
  • The increased rd1 phosducin phosphorylation coincided with increased activation of calcium/calmodulin-activated protein kinase II, which is known to utilize phosducin as a substrate [17].
  • We also demonstrated that STAT3 activation in presumptive rod photoreceptor cells at E18.5 is rapidly downregulated at P0, when Rhodopsin expression starts during retinal development [21].

Analytical, diagnostic and therapeutic context of Pdc

  • Northern blot analysis demonstrates that the mRNA for phosducin is approximately 1.3 kb in both rat pineal and rat retina [14].
  • Western blot analysis detected immunoreactivity both for phosducin and T beta in retinal homogenates of 3-day-old mice [2].
  • Gel filtration analysis of extracts from immature mouse retina showed that phosducin and T beta co-eluted, like the phosducin/T beta gamma complex of adult retina, as a 77-kDa complex, indicating that the phosducin/T beta gamma complex is formed when photoreceptors first synthesize the components of the complex [2].
  • Microinjection of phosducin, however, did not inhibit the fertilization-induced modifications of the zona pellucida and microinjection of beta gamma t did not result in egg activation in the absence of sperm [26].
  • Coculture of transgenic mouse with wild-type mouse or rat retinal cells significantly enhanced transgenic rod photoreceptor survival; this survival-promoting activity was diffusible through a filter, was heat labile, and not present in transgenic retinal cells [27].


  1. Cytoskeleton participation in subcellular trafficking of signal transduction proteins in rod photoreceptor cells. McGinnis, J.F., Matsumoto, B., Whelan, J.P., Cao, W. J. Neurosci. Res. (2002) [Pubmed]
  2. Retinal accumulation of the phosducin/T beta gamma and transducin complexes in developing normal mice and in mice and dogs with inherited retinal degeneration. Lee, R.H., Lieberman, B.S., Lolley, R.N. Exp. Eye Res. (1990) [Pubmed]
  3. Photoreceptor regulated expression of Ca(2+)/calmodulin-dependent protein kinase II in the mouse retina. Liu, L.O., Li, G., McCall, M.A., Cooper, N.G. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  4. Antioxidants reduce cone cell death in a model of retinitis pigmentosa. Komeima, K., Rogers, B.S., Lu, L., Campochiaro, P.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Expression and mutagenesis of mouse rod photoreceptor cGMP phosphodiesterase. Qin, N., Baehr, W. J. Biol. Chem. (1994) [Pubmed]
  6. Rb regulates proliferation and rod photoreceptor development in the mouse retina. Zhang, J., Gray, J., Wu, L., Leone, G., Rowan, S., Cepko, C.L., Zhu, X., Craft, C.M., Dyer, M.A. Nat. Genet. (2004) [Pubmed]
  7. Nrl is required for rod photoreceptor development. Mears, A.J., Kondo, M., Swain, P.K., Takada, Y., Bush, R.A., Saunders, T.L., Sieving, P.A., Swaroop, A. Nat. Genet. (2001) [Pubmed]
  8. Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis. Clarke, G., Goldberg, A.F., Vidgen, D., Collins, L., Ploder, L., Schwarz, L., Molday, L.L., Rossant, J., Szél, A., Molday, R.S., Birch, D.G., McInnes, R.R. Nat. Genet. (2000) [Pubmed]
  9. Crystal structure at 2.4 angstroms resolution of the complex of transducin betagamma and its regulator, phosducin. Gaudet, R., Bohm, A., Sigler, P.B. Cell (1996) [Pubmed]
  10. Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Bowes, C., Li, T., Danciger, M., Baxter, L.C., Applebury, M.L., Farber, D.B. Nature (1990) [Pubmed]
  11. Activation of the prolyl hydroxylase oxygen-sensor results in induction of GLUT1, heme oxygenase-1, and nitric-oxide synthase proteins and confers protection from metabolic inhibition to cardiomyocytes. Wright, G., Higgin, J.J., Raines, R.T., Steenbergen, C., Murphy, E. J. Biol. Chem. (2003) [Pubmed]
  12. Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rd1 mouse retina. Delyfer, M.N., Forster, V., Neveux, N., Picaud, S., Léveillard, T., Sahel, J.A. Mol. Vis. (2005) [Pubmed]
  13. The sequence of the mouse phosducin-encoding gene and its 5'-flanking region. Abe, T., Kikuchi, T., Chang, T., Shinohara, T. Gene (1993) [Pubmed]
  14. Rat pineal gland phosducin: cDNA isolation, nucleotide sequence, and chromosomal assignment in the mouse. Craft, C.M., Lolley, R.N., Seldin, M.F., Lee, R.H. Genomics (1991) [Pubmed]
  15. Phosducin facilitates light-driven transducin translocation in rod photoreceptors. Evidence from the phosducin knockout mouse. Sokolov, M., Strissel, K.J., Leskov, I.B., Michaud, N.A., Govardovskii, V.I., Arshavsky, V.Y. J. Biol. Chem. (2004) [Pubmed]
  16. Probing inner retinal circuits in the rod pathway: a comparison of c-fos activation in mutant mice. Hanzlicek, B.W., Peachey, N.S., Grimm, C., Hagstrom, S.A., Ball, S.L. Vis. Neurosci. (2004) [Pubmed]
  17. Differential modification of phosducin protein in degenerating rd1 retina is associated with constitutively active Ca2+/calmodulin kinase II in rod outer segments. Hauck, S.M., Ekström, P.A., Ahuja-Jensen, P., Suppmann, S., Paquet-Durand, F., van Veen, T., Ueffing, M. Mol. Cell Proteomics (2006) [Pubmed]
  18. Characterization of mice with targeted deletion of glycine receptor alpha 2. Young-Pearse, T.L., Ivic, L., Kriegstein, A.R., Cepko, C.L. Mol. Cell. Biol. (2006) [Pubmed]
  19. Compartment-specific phosphorylation of phosducin in rods underlies adaptation to various levels of illumination. Song, H., Belcastro, M., Young, E.J., Sokolov, M. J. Biol. Chem. (2007) [Pubmed]
  20. The gamma subunit of the rod photoreceptor cGMP phosphodiesterase can modulate the proteolysis of two cGMP binding cGMP-specific phosphodiesterases (PDE6 and PDE5) by caspase-3. Frame, M., Wan, K.F., Tate, R., Vandenabeele, P., Pyne, N.J. Cell. Signal. (2001) [Pubmed]
  21. Downregulation of STAT3 activation is required for presumptive rod photoreceptor cells to differentiate in the postnatal retina. Ozawa, Y., Nakao, K., Shimazaki, T., Takeda, J., Akira, S., Ishihara, K., Hirano, T., Oguchi, Y., Okano, H. Mol. Cell. Neurosci. (2004) [Pubmed]
  22. A 52 kD cytoskeletal protein from retinal rod photoreceptors is related to erythrocyte dematin. Roof, D., Hayes, A., Hardenbergh, G., Adamian, M. Invest. Ophthalmol. Vis. Sci. (1991) [Pubmed]
  23. Phosducin, beta-arrestin and opioid receptor migration. Schulz, R., Wehmeyer, A., Murphy, J., Schulz, K. Eur. J. Pharmacol. (1999) [Pubmed]
  24. Expression of mouse rod photoreceptor cGMP phosphodiesterase gamma subunit in bacteria. Qin, N., Baehr, W. FEBS Lett. (1993) [Pubmed]
  25. The immunolocalization and divergent roles of phosducin and phosducin-like protein in the retina. Thulin, C.D., Howes, K., Driscoll, C.D., Savage, J.R., Rand, T.A., Baehr, W., Willardson, B.M. Mol. Vis. (1999) [Pubmed]
  26. Roles of heterotrimeric and monomeric G proteins in sperm-induced activation of mouse eggs. Moore, G.D., Ayabe, T., Visconti, P.E., Schultz, R.M., Kopf, G.S. Development (1994) [Pubmed]
  27. A diffusible factor from normal retinal cells promotes rod photoreceptor survival in an in vitro model of retinitis pigmentosa. Streichert, L.C., Birnbach, C.D., Reh, T.A. J. Neurobiol. (1999) [Pubmed]
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