May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Targeted Deletion Of Prbp(pde) Prevents Transport Of Prenylated Grk1 And Pde’ To Cone Outer Segments
Author Affiliations & Notes
  • H. Zhang
    Ophthalmology, University of Utah, Salt Lake City, UT
  • S. Li
    Ophthalmology, University of Utah, Salt Lake City, UT
  • J.M. Frederick
    Ophthalmology, University of Utah, Salt Lake City, UT
  • W. Baehr
    Ophthalmology, University of Utah, Salt Lake City, UT
  • Footnotes
    Commercial Relationships  H. Zhang, None; S. Li, None; J.M. Frederick, None; W. Baehr, None.
  • Footnotes
    Support  NIH Grant EY08123; Foundation Fighting Blindness, Inc.; Knights Templar Eye Foundation, Inc.
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 3731. doi:https://doi.org/
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      H. Zhang, S. Li, J.M. Frederick, W. Baehr; Targeted Deletion Of Prbp(pde) Prevents Transport Of Prenylated Grk1 And Pde’ To Cone Outer Segments . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3731. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To identify the role of PrBP in transport of photoreceptor components to the outer segments.

Methods: : Targeted deletion of the Pde6d gene encoding PrBP(PDEΔ); characterization of the PrBP–/– phenotype by immunocytochemistry, histology, western and northern blotting, cone ERGs.

Results: : Although PrBP(PDEΔ) is expressed in many tissues, the Pde6d–/– mouse was viable, fertile and its retina developed normally but suffers slowly progressing rod/cone degeneration. Cone ERGs in the presence of low background light were not recordable. Retinal expression levels of four prenylated rod phototransduction proteins (GRK1, PDEα, PDEß and Tγ) were reduced relative to wildtype littermates. GRK1 and rod PDE subunits were in part mislocalized to rod inner segments while non–prenylated proteins, e.g., rhodopsin and rod Tα, were not affected. GRK1 and cone PDEα’, the catalytic subunit of cone PDE, were nearly undetectable in Pde6d–/– cone outer segments.

Conclusions: : We conclude that absence of PrBP in photoreceptor cells impedes effective transport of prenylated PDE subunits to ROS and completely disrupts transport of farnesylated GRK1 and geranylgeranylated PDEα’ to COS. These results establish a key role of PrBP in transport of prenylated proteins in cones.

Keywords: photoreceptors • transgenics/knock-outs • immunohistochemistry 
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