Title | Deletion of PrBP/delta impedes transport of GRK1 and PDE6 catalytic subunits to photoreceptor outer segments. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Zhang H, Li S, Doan T, Rieke F, Detwiler PB, Frederick JM, Baehr W |
Journal | Proc Natl Acad Sci U S A |
Volume | 104 |
Issue | 21 |
Pagination | 8857-62 |
Date Published | 2007 May 22 |
ISSN | 0027-8424 |
Keywords | Animals, Catalytic Domain, Cyclic Nucleotide Phosphodiesterases, Type 6, Electroretinography, G-Protein-Coupled Receptor Kinase 1, Gene Deletion, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoprene, Phosphoric Diester Hydrolases, Photoreceptor Cells, Vertebrate, Protein Transport |
Abstract | 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. |
DOI | 10.1073/pnas.0701681104 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 17496142 |
PubMed Central ID | PMC1885592 |
Grant List | EY02048 / EY / NEI NIH HHS / United States EY08123 / EY / NEI NIH HHS / United States R01 EY011850 / EY / NEI NIH HHS / United States EY11850 / EY / NEI NIH HHS / United States R01 EY002048 / EY / NEI NIH HHS / United States R01 EY008123 / EY / NEI NIH HHS / United States |