@article{266,
  keywords = {Animals, Mice, Mice, Inbred C57BL, Mice, Knockout, G-Protein-Coupled Receptor Kinase 1, Catalytic Domain, Cyclic Nucleotide Phosphodiesterases, Type 6, Electroretinography, Gene Deletion, Neoprene, Phosphoric Diester Hydrolases, Photoreceptor Cells, Vertebrate, Protein Transport},
  author = {H Zhang and S Li and T Doan and F Rieke and P Detwiler and J Frederick and W Baehr},
  title = {Deletion of PrBP/delta impedes transport of GRK1 and PDE6 catalytic subunits to photoreceptor outer segments.},
  abstract = {<p>The mouse Pde6d gene encodes a ubiquitous prenyl binding protein, termed PrBP/delta, of largely unknown physiological function. PrBP/delta was originally identified as a putative rod cGMP phosphodiesterase (PDE6) subunit in the retina, where it is relatively abundant. To investigate the consequences of Pde6d deletion in retina, we generated a Pde6d(-/-) mouse by targeted recombination. Although manifesting reduced body weight, the Pde6d(-/-) mouse was viable and fertile and its retina developed normally. Immunocytochemistry showed that farnesylated rhodopsin kinase (GRK1) and prenylated rod PDE6 catalytic subunits partially mislocalized in Pde6d(-/-) rods, whereas rhodopsin was unaffected. In Pde6d(-/-) rod single-cell recordings, sensitivity to single photons was increased and saturating flash responses were prolonged. Pde6d(-/-) scotopic paired-flash electroretinograms indicated a delay in recovery of the dark state, likely due to reduced levels of GRK1 in rod outer segments. In Pde6d(-/-) cone outer segments, GRK1 and cone PDE6alpha' were present at very low levels and the photopic b-wave amplitudes were reduced by 70%. Thus the absence of PrBP/delta in retina impairs transport of prenylated proteins, particularly GRK1 and cone PDE, to rod and cone outer segments, resulting in altered photoreceptor physiology and a phenotype of a slowly progressing rod/cone dystrophy.</p>
},
  year = {2007},
  journal = {Proc Natl Acad Sci U S A},
  volume = {104},
  pages = {8857-62},
  month = {2007 May 22},
  issn = {0027-8424},
  doi = {10.1073/pnas.0701681104},
  language = {eng},
}