May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Kinesin-II Regulates Transport of Membrane-Associated Proteins to the Cone Photoreceptor Outer Segments
Author Affiliations & Notes
  • P. Avasthi
    University of Utah, Salt Lake CIty, Utah
    Neuroscience Program,
  • Y. Le
    Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
  • D. Williams
    Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, California
  • J. M. Frederick
    University of Utah, Salt Lake CIty, Utah
    Department of Ophthalmology and Visual Sciences,
  • W. Baehr
    University of Utah, Salt Lake CIty, Utah
    Departments of Ophthalmology and Visual Sciences, Biology, and Neurobiology and Anatomy,
  • Footnotes
    Commercial Relationships  P. Avasthi, None; Y. Le, None; D. Williams, None; J.M. Frederick, None; W. Baehr, None.
  • Footnotes
    Support  1RO1 EY08123; 1P30 EY014800; Foundation Fighting Blindness, Inc.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1264. doi:https://doi.org/
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    • Get Citation

      P. Avasthi, Y. Le, D. Williams, J. M. Frederick, W. Baehr; Kinesin-II Regulates Transport of Membrane-Associated Proteins to the Cone Photoreceptor Outer Segments. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1264. doi: https://doi.org/.

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

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Abstract

Purpose: : Kinesin-II is an anterograde molecular motor localized to the connecting cilium of the mammalian photoreceptor. The role of kinesin-II in cone intraflagellar transport (IFT) was examined by cell-specific deletion of Kif3a, the motor subunit of Kinesin-II.

Methods: : For cone-specific Kif3a deletion, Kif3a flox/flox mice were bred with transgenic mice expressing Cre recombinase under the control of the human red/green pigment (HRGP) promoter. Consequences of Kif3a deletion were analyzed by confocal immunocytochemistry, immunoblotting, ERG and quantitative RT/PCR.

Results: : Deletion of cone Kif3a resulted in a significant mislocalization of S- and M/L- cone opsins (normally in the outer segments) to the inner segments, outer nuclear layer and synaptic terminals. Rhodopsin kinase (GRK1) and guanylate cyclase (GC1), which are expressed in both rods and cones, were significantly reduced in cone outer segments. Finally, cone-specific phosphodiesterase (cPDE) and transducin were virtually absent from Kif3a-deleted photoreceptors. Real time PCR shows that the decrease is not due to downregulation of mRNA expression and is therefore likely a result of posttranslational degradation. Loss of these proteins essential for phototransduction resulted in complete absence of a light-stimulated response detected by photopic electroretinogram. While GRK1, GC1, cone PDE, and cone transducin are virtually absent from cone outer segments, cone arrestin and the synaptic terminal proteins complexin IV, bassoon and SV2 show normal localizations.

Conclusions: : Our results suggest that kinesin-II is responsible for intraflagellar transport of the integral membrane proteins S-opsin, M/L-opsin, GC1, as well as membrane-associated phototransduction proteins, to the cone outer segments.

Keywords: photoreceptors • transgenics/knock-outs • color vision 
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